Skip to main content

Curcumin: Structure, Biology and Clinical Applications

  • Chapter
  • First Online:
Nutrition, Diet and Cancer

Abstract

Curcumin, the principal polyphenolic curcuminoid derived from the rhizome Curcuma longa, is present in an Indian spice, turmeric. Curcumin possesses antitumor, antioxidant, and anti-inflammatory properties, and has been studied as a cancer chemopreventive agent. Curcumin is extensively studied, evaluated and accepted for its wide range of medicinal properties. The therapeutic activities of curcumin for a wide variety of diseases such as diabetes, allergies, arthritis and other chronic and inflammatory diseases have been known for a long time. The mechanisms of therapeutic action of curcumin include inhibition of several cell signaling pathways at multiple levels, immune-modulation, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases and effects on angiogenesis and metastasis. It has ability to affect gene transcription and induce cell cycle arrest and apoptosis. Although curcumin is a highly pleiotropic molecule with an excellent safety profile targeting multiple diseases, it could not achieve its optimum therapeutic outcome in clinical trials, largely due to its low solubility and poor bioavailability. Based on the results of the clinical trials, curcumin can be developed as a therapeutic drug through improvement in formulations or delivery systems, enabling its enhanced absorption and cellular uptake. In this review article, we provide a comprehensive outlook for the therapeutic potential of curcumin, and discuss future strategies and potential challenges involved in the use of curcumin.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aggarwal BB, Shishodia S (2006) Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol 71:1397–1421

    Article  CAS  PubMed  Google Scholar 

  • Aggarwal BB, Sethi G, Ahn KS, Sandur SK, Pandey MK, Kunnumakkara AB, Sung B, Ichikawa H (2006a) Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: modern target but ancient solution. Ann N Y Acad Sci 1091:151–169

    Article  CAS  PubMed  Google Scholar 

  • Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G (2006b) Inflammation and cancer: how hot is the link? Biochem Pharmacol 72:1605–1621

    Article  CAS  PubMed  Google Scholar 

  • Aggarwal S, Ichikawa H, Takada Y, Sandur SK, Shishodia S, Aggarwal BB (2006c) Curcumin (diferuloylmethane) down-regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IkappaBalpha kinase and Akt activation. Mol Pharmacol 69:195–206

    CAS  PubMed  Google Scholar 

  • Aggarwal BB, Banerjee S, Bharadwaj U, Sung B, Shishodia S, Sethi G (2007a) Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines. Biochem Pharmacol 73:1024–1032

    Article  CAS  PubMed  Google Scholar 

  • Aggarwal BB, Sundaram C, Malani N, Ichikawa H (2007b) Curcumin: the Indian solid gold. Adv Exp Med Biol 595:1–75

    Article  PubMed  Google Scholar 

  • Alessandrini A, Chiaur DS, Pagano M (1997) Regulation of the cyclin-dependent kinase inhibitor p27 by degradation and phosphorylation. Leukemia 11:342–345

    Article  CAS  PubMed  Google Scholar 

  • Almasan A, Yin Y, Kelly RE, Lee EY, Bradley A, Li W, Bertino JR, Wahl GM (1995) Deficiency of retinoblastoma protein leads to inappropriate S-phase entry, activation of E2F-responsive genes, and apoptosis. Proc Natl Acad Sci U S A 92:5436–5440

    Article  CAS  PubMed  Google Scholar 

  • Alwi I, Santoso T, Suyono S, Sutrisna B, Suyatna FD, Kresno SB, Ernie S (2008) The effect of curcumin on lipid level in patients with acute coronary syndrome. Acta Med Indones 40:201–210

    PubMed  Google Scholar 

  • Arellano M, Moreno S (1997) Regulation of CDK/cyclin complexes during the cell cycle. Int J Biochem Cell Biol 29:559–573

    Article  CAS  PubMed  Google Scholar 

  • Artandi SE, DePinho RA (2000) Mice without telomerase: what can they teach us about human cancer? Nat Med 6:852–855

    Article  CAS  PubMed  Google Scholar 

  • Artavanis-Tsakonas S, Muskavitch MA (2010) Notch: the past, the present, and the future. Curr Top Dev Biol 92:1–29

    Article  CAS  PubMed  Google Scholar 

  • Artavanis-Tsakonas S, Matsuno K, Fortini ME (1995) Notch signaling. Science 268:225–232

    Article  CAS  PubMed  Google Scholar 

  • Arthan D, Hong SK, Park JI (2010) Leukemia inhibitory factor can mediate Ras/Raf/MEK/ERK-induced growth inhibitory signaling in medullary thyroid cancer cells. Cancer Lett 297:31–41

    Article  CAS  PubMed  Google Scholar 

  • Arun N, Nalini N (2002) Efficacy of turmeric on blood sugar and polyol pathway in diabetic albino rats. Plant Foods Hum Nutr 57:41–52

    Article  CAS  PubMed  Google Scholar 

  • Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, Blackie C, Chang L, McMurtrey AE, Hebert A, DeForge L, Koumenis IL, Lewis D, Harris L, Bussiere J, Koeppen H, Shahrokh Z, Schwall RH (1999) Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 104:155–162

    Article  CAS  PubMed  Google Scholar 

  • Assoian RK (1997) Control of the G1 phase cyclin-dependent kinases by mitogenic growth factors and the extracellular matrix. Cytokine Growth Factor Rev 8:165–170

    Article  CAS  PubMed  Google Scholar 

  • Attwooll C, Lazzerini Denchi E, Helin K (2004) The E2F family: specific functions and overlapping interests. EMBO J 23:4709–4716

    Article  CAS  PubMed  Google Scholar 

  • Azuine MA, Bhide SV (1994) Adjuvant chemoprevention of experimental cancer: catechin and dietary turmeric in forestomach and oral cancer models. J Ethnopharmacol 44:211–217

    Article  CAS  PubMed  Google Scholar 

  • Bae MK, Kim SH, Jeong JW, Lee YM, Kim HS, Kim SR, Yun I, Bae SK, Kim KW (2006) Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1. Oncol Rep 15:1557–1562

    CAS  PubMed  Google Scholar 

  • Bailey JM, Singh PK, Hollingsworth MA (2007) Cancer metastasis facilitated by developmental pathways: Sonic hedgehog, Notch, and bone morphogenic proteins. J Cell Biochem 102:829–839

    Article  CAS  PubMed  Google Scholar 

  • Balasubramanian S, Eckert RL (2007) Curcumin suppresses AP1 transcription factor-dependent differentiation and activates apoptosis in human epidermal keratinocytes. J Biol Chem 282:6707–6715

    Article  CAS  PubMed  Google Scholar 

  • Balogun E, Foresti R, Green CJ, Motterlini R (2003a) Changes in temperature modulate heme oxygenase-1 induction by curcumin in renal epithelial cells. Biochem Biophys Res Commun 308:950–955

    Article  CAS  PubMed  Google Scholar 

  • Balogun E, Hoque M, Gong P, Killeen E, Green CJ, Foresti R, Alam J, Motterlini R (2003b) Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem J 371:887–895

    Article  CAS  PubMed  Google Scholar 

  • Banning A, Deubel S, Kluth D, Zhou Z, Brigelius-Flohe R (2005) The GI-GPx gene is a target for Nrf2. Mol Cell Biol 25:4914–4923

    Article  CAS  PubMed  Google Scholar 

  • Barker N, Clevers H (2000) Catenins, Wnt signaling and cancer. Bioessays 22:961–965

    Article  CAS  PubMed  Google Scholar 

  • Bemis DL, Katz AE, Buttyan R (2006) Clinical trials of natural products as chemopreventive agents for prostate cancer. Expert Opin Investig Drugs 15:1191–1200

    Article  CAS  PubMed  Google Scholar 

  • Bengmark S (2006) Curcumin, an atoxic antioxidant and natural NFkappaB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases. JPEN J Parenter Enteral Nutr 30:45–51

    Article  CAS  PubMed  Google Scholar 

  • Bengmark S, Mesa MD, Gil A (2009) Plant-derived health: the effects of turmeric and curcuminoids. Nutr Hosp 24:273–281

    CAS  PubMed  Google Scholar 

  • Beresford SA, Davies MA, Gallick GE, Donato NJ (2001) Differential effects of phosphatidylinositol-3/Akt-kinase inhibition on apoptotic sensitization to cytokines in LNCaP and PCc-3 prostate cancer cells. J Interferon Cytokine Res 21:313–322

    Article  CAS  PubMed  Google Scholar 

  • Bhattacharyya S, Mandal D, Saha B, Sen GS, Das T, Sa G (2007) Curcumin prevents tumor-induced T cell apoptosis through Stat-5a-mediated Bcl-2 induction. J Biol Chem 282:15954–15964

    Article  CAS  PubMed  Google Scholar 

  • Bigas A, Robert-Moreno A, Espinosa L (2010) The Notch pathway in the developing hematopoietic system. Int J Dev Biol 54:1175–1188

    Article  CAS  PubMed  Google Scholar 

  • Bill MA, Bakan C, Benson DM Jr, Fuchs J, Young G, Lesinski GB (2009) Curcumin induces proapoptotic effects against human melanoma cells and modulates the cellular response to immunotherapeutic cytokines. Mol Cancer Ther 8:2726–2735

    Article  CAS  PubMed  Google Scholar 

  • Blasco MA (2002) Telomerase beyond telomeres. Nat Rev Cancer 2:627–633

    Article  CAS  PubMed  Google Scholar 

  • Blasius R, Reuter S, Henry E, Dicato M, Diederich M (2006) Curcumin regulates signal transducer and activator of transcription (STAT) expression in K562 cells. Biochem Pharmacol 72:1547–1554

    Article  CAS  PubMed  Google Scholar 

  • Bray SJ (2006) Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol 7:678–689

    Article  CAS  PubMed  Google Scholar 

  • Brennan C, Momota H, Hambardzumyan D, Ozawa T, Tandon A, Pedraza A, Holland E (2009) Glioblastoma subclasses can be defined by activity among signal transduction pathways and associated genomic alterations. PLoS One 4:e7752

    Article  PubMed  CAS  Google Scholar 

  • Brugarolas J, Moberg K, Boyd SD, Taya Y, Jacks T, Lees JA (1999) Inhibition of cyclin-dependent kinase 2 by p21 is necessary for retinoblastoma protein-mediated G1 arrest after gamma-irradiation. Proc Natl Acad Sci U S A 96:1002–1007

    Article  CAS  PubMed  Google Scholar 

  • Cai K, Qi D, Hou X, Wang O, Chen J, Deng B, Qian L, Liu X, Le Y (2011) MCP-1 upregulates amylin expression in murine pancreatic beta cells through ERK/JNK-AP1 and NF-kappaB related signaling pathways independent of CCR2. PLoS One 6:e19559

    Article  CAS  PubMed  Google Scholar 

  • Cantley LC (2002) The phosphoinositide 3-kinase pathway. Science 296:1655–1657

    Article  CAS  PubMed  Google Scholar 

  • Carnero A, Hannon GJ (1998) The INK4 family of CDK inhibitors. Curr Top Microbiol Immunol 227:43–55

    Article  CAS  PubMed  Google Scholar 

  • Cerdan C, Bhatia M (2010) Novel roles for Notch, Wnt and Hedgehog in hematopoesis derived from human pluripotent stem cells. Int J Dev Biol 54:955–963

    Article  CAS  PubMed  Google Scholar 

  • Chen YR, Tan TH (1998) Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin. Oncogene 17:173–178

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Thakkar H, Tyan F, Gim S, Robinson H, Lee C, Pandey SK, Nwokorie C, Onwudiwe N, Srivastava RK (2001) Constitutively active Akt is an important regulator of TRAIL sensitivity in prostate cancer. Oncogene 20:6073–6083

    Article  CAS  PubMed  Google Scholar 

  • Chen A, Xu J, Johnson AC (2006) Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1. Oncogene 25:278–287

    PubMed  Google Scholar 

  • Chen Y, Shu W, Chen W, Wu Q, Liu H, Cui G (2007) Curcumin, both histone deacetylase and p300/CBP-specific inhibitor, represses the activity of nuclear factor kappa B and Notch 1 in Raji cells. Basic Clin Pharmacol Toxicol 101:427–433

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Imanaka N, Griffin JD (2010) Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion. Br J Cancer 102:351–360

    Article  CAS  PubMed  Google Scholar 

  • Cheng P, Zlobin A, Volgina V, Gottipati S, Osborne B, Simel EJ, Miele L, Gabrilovich DI (2001) Notch-1 regulates NF-kappaB activity in hemopoietic progenitor cells. J Immunol 167:4458–4467

    CAS  PubMed  Google Scholar 

  • Cheng H, Liu W, Ai X (2005) Protective effect of curcumin on myocardial ischemia reperfusion injury in rats. Zhong Yao Cai 28:920–922

    PubMed  Google Scholar 

  • Chiarle R, Budel LM, Skolnik J, Frizzera G, Chilosi M, Corato A, Pizzolo G, Magidson J, Montagnoli A, Pagano M, Maes B, De Wolf-Peeters C, Inghirami G (2000) Increased proteasome degradation of cyclin-dependent kinase inhibitor p27 is associated with a decreased overall survival in mantle cell lymphoma. Blood 95:619–626

    CAS  PubMed  Google Scholar 

  • Chilosi M, Chiarle R, Lestani M, Menestrina F, Montagna L, Ambrosetti A, Prolla G, Pizzolo G, Doglioni C, Piva R, Pagano M, Inghirami G (2000) Low expression of p27 and low proliferation index do not correlate in hairy cell leukaemia. Br J Haematol 111:263–271

    Article  CAS  PubMed  Google Scholar 

  • Chirnomas D, Taniguchi T, de la Vega M, Vaidya AP, Vasserman M, Hartman AR, Kennedy R, Foster R, Mahoney J, Seiden MV, D’Andrea AD (2006) Chemosensitization to cisplatin by inhibitors of the Fanconi anemia/BRCA pathway. Mol Cancer Ther 5:952–961

    Article  CAS  PubMed  Google Scholar 

  • Chu I, Sun J, Arnaout A, Kahn H, Hanna W, Narod S, Sun P, Tan CK, Hengst L, Slingerland J (2007) p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2. Cell 128:281–294

    Article  CAS  PubMed  Google Scholar 

  • Classon M, Harlow E (2002) The retinoblastoma tumour suppressor in development and cancer. Nat Rev Cancer 2:910–917

    Article  CAS  PubMed  Google Scholar 

  • Clevers H (2004) Wnt breakers in colon cancer. Cancer Cell 5:5–6

    Article  CAS  PubMed  Google Scholar 

  • Clevers H (2006) Wnt/beta-catenin signaling in development and disease. Cell 127:469–480

    Article  CAS  PubMed  Google Scholar 

  • Cohen MM Jr (2003) The hedgehog signaling network. Am J Med Genet A 123A:5–28

    Article  PubMed  Google Scholar 

  • Cohen P, Frame S (2001) The renaissance of GSK3. Nat Rev Mol Cell Biol 2:769–776

    Article  CAS  PubMed  Google Scholar 

  • Cohen B, Shimizu M, Izrailit J, Ng NF, Buchman Y, Pan JG, Dering J, Reedijk M (2010) Cyclin D1 is a direct target of JAG1-mediated Notch signaling in breast cancer. Breast Cancer Res Treat 123:113–124

    Article  CAS  PubMed  Google Scholar 

  • Cohly HH, Taylor A, Angel MF, Salahudeen AK (1998) Effect of turmeric, turmerin and curcumin on H2O2-induced renal epithelial (LLC-PK1) cell injury. Free Radic Biol Med 24:49–54

    Article  CAS  PubMed  Google Scholar 

  • D’Altri T, Gonzalez J, Aifantis I, Espinosa L, Bigas A (2011) Hes1 expression and CYLD repression are essential events downstream of Notch1 in T-cell leukemia. Cell Cycle 10:1031–1036

    Article  PubMed  CAS  Google Scholar 

  • Darnell JE Jr, Kerr IM, Stark GR (1994) Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264:1415–1421

    Article  CAS  PubMed  Google Scholar 

  • Das D, Lanner F, Main H, Andersson ER, Bergmann O, Sahlgren C, Heldring N, Hermanson O, Hansson EM, Lendahl U (2010) Notch induces cyclin-D1-dependent proliferation during a specific temporal window of neural differentiation in ES cells. Dev Biol 348:153–166

    Article  CAS  PubMed  Google Scholar 

  • Dasari A, Messersmith WA (2010) New strategies in colorectal cancer: biomarkers of response to epidermal growth factor receptor monoclonal antibodies and potential therapeutic targets in phosphoinositide 3-kinase and mitogen-activated protein kinase pathways. Clin Cancer Res 16:3811–3818

    Article  CAS  PubMed  Google Scholar 

  • Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91:231–241

    Article  CAS  PubMed  Google Scholar 

  • Datta SR, Brunet A, Greenberg ME (1999) Cellular survival: a play in three Akts. Genes Dev 13:2905–2927

    Article  CAS  PubMed  Google Scholar 

  • Davies MA, Lu Y, Sano T, Fang X, Tang P, LaPushin R, Koul D, Bookstein R, Stokoe D, Yung WK, Mills GB, Steck PA (1998) Adenoviral transgene expression of MMAC/PTEN in human glioma cells inhibits Akt activation and induces anoikis. Cancer Res 58:5285–5290

    CAS  PubMed  Google Scholar 

  • Decock J, Thirkettle S, Wagstaff L, Edwards DR (2011) Matrix metalloproteinases: protective roles in cancer. J Cell Mol Med 15:1254–1265

    Article  CAS  PubMed  Google Scholar 

  • Deeb D, Xu YX, Jiang H, Gao X, Janakiraman N, Chapman RA, Gautam SC (2003) Curcumin (diferuloyl-methane) enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in LNCaP prostate cancer cells. Mol Cancer Ther 2:95–103

    CAS  PubMed  Google Scholar 

  • Deeb DD, Jiang H, Gao X, Divine G, Dulchavsky SA, Gautam SC (2005) Chemosensitization of hormone-refractory prostate cancer cells by curcumin to TRAIL-induced apoptosis. J Exp Ther Oncol 5:81–91

    CAS  PubMed  Google Scholar 

  • DeGregori J, Leone G, Miron A, Jakoi L, Nevins JR (1997) Distinct roles for E2F proteins in cell growth control and apoptosis. Proc Natl Acad Sci U S A 94:7245–7250

    Article  CAS  PubMed  Google Scholar 

  • Deryugina EI, Quigley JP (2010) Pleiotropic roles of matrix metalloproteinases in tumor angiogenesis: contrasting, overlapping and compensatory functions. Biochim Biophys Acta 1803:103–120

    Article  CAS  PubMed  Google Scholar 

  • Dikic I, Schmidt MH (2010) Notch: implications of endogenous inhibitors for therapy. Bioessays 32:481–487

    Article  CAS  PubMed  Google Scholar 

  • Dikshit M, Rastogi L, Shukla R, Srimal RC (1995) Prevention of ischaemia-induced biochemical changes by curcumin & quinidine in the cat heart. Indian J Med Res 101:31–35

    CAS  PubMed  Google Scholar 

  • Dikshit P, Goswami A, Mishra A, Chatterjee M, Jana NR (2006) Curcumin induces stress response, neurite outgrowth and prevent NF-kappaB activation by inhibiting the proteasome function. Neurotox Res 9:29–37

    Article  CAS  PubMed  Google Scholar 

  • Divya CS, Pillai MR (2006) Antitumor action of curcumin in human papillomavirus associated cells involves downregulation of viral oncogenes, prevention of NFkB and AP-1 translocation, and modulation of apoptosis. Mol Carcinog 45:320–332

    Article  CAS  PubMed  Google Scholar 

  • Dodge ME, Lum L (2011) Drugging the cancer stem cell compartment: lessons learned from the hedgehog and Wnt signal transduction pathways. Annu Rev Pharmacol Toxicol 51:289–310

    Article  CAS  PubMed  Google Scholar 

  • Dorai T, Gehani N, Katz A (2000) Therapeutic potential of curcumin in human prostate cancer. II. Curcumin inhibits tyrosine kinase activity of epidermal growth factor receptor and depletes the protein. Mol Urol 4:1–6

    CAS  PubMed  Google Scholar 

  • Downward J (2004) PI 3-kinase, Akt and cell survival. Semin Cell Dev Biol 15:177–182

    Article  CAS  PubMed  Google Scholar 

  • Dreesen O, Brivanlou AH (2007) Signaling pathways in cancer and embryonic stem cells. Stem Cell Rev 3:7–17

    Article  CAS  PubMed  Google Scholar 

  • D’Souza B, Miyamoto A, Weinmaster G (2008) The many facets of Notch ligands. Oncogene 27:5148–5167

    Article  PubMed  CAS  Google Scholar 

  • Du C, Fang M, Li Y, Li L, Wang X (2000) Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102:33–42

    Article  CAS  PubMed  Google Scholar 

  • Du B, Jiang L, Xia Q, Zhong L (2006) Synergistic inhibitory effects of curcumin and 5-fluorouracil on the growth of the human colon cancer cell line HT-29. Chemotherapy 52:23–28

    Article  CAS  PubMed  Google Scholar 

  • Dyson N (1998) The regulation of E2F by pRB-family proteins. Genes Dev 12:2245–2262

    Article  CAS  PubMed  Google Scholar 

  • Easton J, Wei T, Lahti JM, Kidd VJ (1998) Disruption of the cyclin D/cyclin-dependent kinase/INK4/retinoblastoma protein regulatory pathway in human neuroblastoma. Cancer Res 58:2624–2632

    CAS  PubMed  Google Scholar 

  • Elamin MH, Shinwari Z, Hendrayani SF, Al-Hindi H, Al-Shail E, Khafaga Y, Al-Kofide A, Aboussekhra A (2010) Curcumin inhibits the Sonic Hedgehog signaling pathway and triggers apoptosis in medulloblastoma cells. Mol Carcinog 49:302–314

    CAS  PubMed  Google Scholar 

  • el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B (1993) WAF1, a potential mediator of p53 tumor suppression. Cell 75:817–825

    Article  CAS  PubMed  Google Scholar 

  • Evans T, Rosenthal ET, Youngblom J, Distel D, Hunt T (1983) Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell 33:389–396

    Article  CAS  PubMed  Google Scholar 

  • Farnie G, Clarke RB (2007) Mammary stem cells and breast cancer–role of Notch signalling. Stem Cell Rev 3:169–175

    Article  CAS  PubMed  Google Scholar 

  • Fero ML, Randel E, Gurley KE, Roberts JM, Kemp CJ (1998) The murine gene p27Kip1 is haplo-insufficient for tumour suppression. Nature 396:177–180

    Article  CAS  PubMed  Google Scholar 

  • Ferrari-Toninelli G, Bonini SA, Uberti D, Buizza L, Bettinsoli P, Poliani PL, Facchetti F, Memo M (2010) Targeting Notch pathway induces growth inhibition and differentiation of neuroblastoma cells. Neuro Oncol 12:1231–1243

    CAS  PubMed  Google Scholar 

  • Ferres-Marco D, Gutierrez-Garcia I, Vallejo DM, Bolivar J, Gutierrez-Avino FJ, Dominguez M (2006) Epigenetic silencers and Notch collaborate to promote malignant tumours by Rb silencing. Nature 439:430–436

    Article  CAS  PubMed  Google Scholar 

  • Folkman J (2003) Fundamental concepts of the angiogenic process. Curr Mol Med 3:643–651

    Article  CAS  PubMed  Google Scholar 

  • Frautschy SA, Cole GM (2010) Why pleiotropic interventions are needed for Alzheimer’s disease. Mol Neurobiol 41:392–409

    Article  CAS  PubMed  Google Scholar 

  • Garg AK, Buchholz TA, Aggarwal BB (2005) Chemosensitization and radiosensitization of tumors by plant polyphenols. Antioxid Redox Signal 7:1630–1647

    Article  CAS  PubMed  Google Scholar 

  • Girard F, Strausfeld U, Fernandez A, Lamb NJ (1991) Cyclin A is required for the onset of DNA replication in mammalian fibroblasts. Cell 67:1169–1179

    Article  CAS  PubMed  Google Scholar 

  • Giri RK, Rajagopal V, Kalra VK (2004) Curcumin, the active constituent of turmeric, inhibits amyloid peptide-induced cytochemokine gene expression and CCR5-mediated chemotaxis of THP-1 monocytes by modulating early growth response-1 transcription factor. J Neurochem 91:1199–1210

    Article  CAS  PubMed  Google Scholar 

  • Glienke W, Maute L, Wicht J, Bergmann L (2010) Curcumin inhibits constitutive STAT3 phosphorylation in human pancreatic cancer cell lines and downregulation of survivin/BIRC5 gene expression. Cancer Invest 28:166–171

    Article  CAS  PubMed  Google Scholar 

  • Glotzer M, Murray AW, Kirschner MW (1991) Cyclin is degraded by the ubiquitin pathway. Nature 349:132–138

    Article  CAS  PubMed  Google Scholar 

  • Goel A, Aggarwal BB (2010) Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer 62:919–930

    Article  CAS  PubMed  Google Scholar 

  • Gong J, Ardelt B, Traganos F, Darzynkiewicz Z (1994) Unscheduled expression of cyclin B1 and cyclin E in several leukemic and solid tumor cell lines. Cancer Res 54:4285–4288

    CAS  PubMed  Google Scholar 

  • Gopinath D, Ahmed MR, Gomathi K, Chitra K, Sehgal PK, Jayakumar R (2004) Dermal wound healing processes with curcumin incorporated collagen films. Biomaterials 25:1911–1917

    Article  CAS  PubMed  Google Scholar 

  • Grimmler M, Wang Y, Mund T, Cilensek Z, Keidel EM, Waddell MB, Jakel H, Kullmann M, Kriwacki RW, Hengst L (2007) Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases. Cell 128:269–280

    Article  CAS  PubMed  Google Scholar 

  • Guo S, Liu M, Gonzalez-Perez RR (2011) Role of Notch and its oncogenic signaling crosstalk in breast cancer. Biochim Biophys Acta 1815:197–213

    CAS  PubMed  Google Scholar 

  • Haas K, Johannes C, Geisen C, Schmidt T, Karsunky H, Blass-Kampmann S, Obe G, Moroy T (1997) Malignant transformation by cyclin E and Ha-Ras correlates with lower sensitivity towards induction of cell death but requires functional Myc and CDK4. Oncogene 15:2615–2623

    Article  CAS  PubMed  Google Scholar 

  • Haase MG, Klawitter A, Bierhaus A, Yokoyama KK, Kasper M, Geyer P, Baumann M, Baretton GB (2008) Inactivation of AP1 proteins by a nuclear serine protease precedes the onset of radiation-induced fibrosing alveolitis. Radiat Res 169:531–542

    Article  CAS  PubMed  Google Scholar 

  • Hahn WC, Weinberg RA (2002) Modelling the molecular circuitry of cancer. Nat Rev Cancer 2:331–341

    Article  CAS  PubMed  Google Scholar 

  • Hall M, Peters G (1996) Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Adv Cancer Res 68:67–108

    Article  CAS  PubMed  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  CAS  PubMed  Google Scholar 

  • Harper JW, Elledge SJ, Keyomarsi K, Dynlacht B, Tsai LH, Zhang P, Dobrowolski S, Bai C, Connell-Crowley L, Swindell E et al (1995) Inhibition of cyclin-dependent kinases by p21. Mol Biol Cell 6:387–400

    CAS  PubMed  Google Scholar 

  • Harrison H, Farnie G, Brennan KR, Clarke RB (2010) Breast cancer stem cells: something out of notching? Cancer Res 70:8973–8976

    Article  CAS  PubMed  Google Scholar 

  • Hazan-Halevy I, Harris D, Liu Z, Liu J, Li P, Chen X, Shanker S, Ferrajoli A, Keating MJ, Estrov Z (2010) STAT3 is constitutively phosphorylated on serine 727 residues, binds DNA, and activates transcription in CLL cells. Blood 115:2852–2863

    Article  CAS  PubMed  Google Scholar 

  • He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW (1998) Identification of c-MYC as a target of the APC pathway. Science 281:1509–1512

    Article  CAS  PubMed  Google Scholar 

  • HemaIswarya S, Doble M (2006) Potential synergism of natural products in the treatment of cancer. Phytother Res 20:239–249

    Article  CAS  PubMed  Google Scholar 

  • Hengst L, Reed SI (1996) Translational control of p27Kip1 accumulation during the cell cycle. Science 271:1861–1864

    Article  CAS  PubMed  Google Scholar 

  • Hengst L, Reed SI (1998) Inhibitors of the Cip/Kip family. Curr Top Microbiol Immunol 227:25–41

    Article  CAS  PubMed  Google Scholar 

  • Hershko DD, Shapira M (2006) Prognostic role of p27Kip1 deregulation in colorectal cancer. Cancer 107:668–675

    Article  CAS  PubMed  Google Scholar 

  • Howells LM, Sale S, Sriramareddy SN, Irving GR, Jones DJ, Ottley CJ, Pearson DG, Mann CD, Manson MM, Berry DP, Gescher A, Steward WP, Brown K (2010) Curcumin ameliorates oxaliplatin-induced chemoresistance in HCT116 colorectal cancer cells in vitro and in vivo. Int J Cancer 129(2):476–486

    Article  PubMed  CAS  Google Scholar 

  • Hsieh A, Ellsworth R, Hsieh D (2011) Hedgehog/GLI1 regulates IGF dependent malignant behaviors in glioma stem cells. J Cell Physiol 226:1118–1127

    Article  CAS  PubMed  Google Scholar 

  • Hua H, Li M, Luo T, Yin Y, Jiang Y (2011) Matrix metalloproteinases in tumorigenesis: an evolving paradigm. Cell Mol Life Sci 68(23):3853–3868

    Article  CAS  PubMed  Google Scholar 

  • Huang TS, Lee SC, Lin JK (1991) Suppression of c-Jun/AP-1 activation by an inhibitor of tumor promotion in mouse fibroblast cells. Proc Natl Acad Sci U S A 88:5292–5296

    Article  CAS  PubMed  Google Scholar 

  • Huang P, Han J, Hui L (2010) MAPK signaling in inflammation-associated cancer development. Protein Cell 1:218–226

    Article  CAS  PubMed  Google Scholar 

  • Hunter T, Pines J (1994) Cyclins and cancer. II: cyclin D and CDK inhibitors come of age. Cell 79:573–582

    Article  CAS  PubMed  Google Scholar 

  • Iida H, Towatari M, Tanimoto M, Morishita Y, Kodera Y, Saito H (1997) Overexpression of cyclin E in acute myelogenous leukemia. Blood 90:3707–3713

    CAS  PubMed  Google Scholar 

  • Jaiswal AS, Marlow BP, Gupta N, Narayan S (2002) Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Oncogene 21:8414–8427

    Article  CAS  PubMed  Google Scholar 

  • Jang MS, Miao H, Carlesso N, Shelly L, Zlobin A, Darack N, Qin JZ, Nickoloff BJ, Miele L (2004) Notch-1 regulates cell death independently of differentiation in murine erythroleukemia cells through multiple apoptosis and cell cycle pathways. J Cell Physiol 199:418–433

    Article  CAS  PubMed  Google Scholar 

  • Jeffrey PD, Russo AA, Polyak K, Gibbs E, Hurwitz J, Massague J, Pavletich NP (1995) Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex. Nature 376:313–320

    Article  CAS  PubMed  Google Scholar 

  • Jones EA, Shoskes DA (2000) The effect of mycophenolate mofetil and polyphenolic bioflavonoids on renal ischemia reperfusion injury and repair. J Urol 163:999–1004

    Article  CAS  PubMed  Google Scholar 

  • Jones EA, Shahed A, Shoskes DA (2000) Modulation of apoptotic and inflammatory genes by bioflavonoids and angiotensin II inhibition in ureteral obstruction. Urology 56:346–351

    Article  CAS  PubMed  Google Scholar 

  • Jung EM, Park JW, Choi KS, Park JW, Lee HI, Lee KS, Kwon TK (2006) Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through CHOP-independent DR5 upregulation. Carcinogenesis 27(10):2008–2017

    Article  CAS  PubMed  Google Scholar 

  • Kakarala M, Wicha MS (2008) Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy. J Clin Oncol 26:2813–2820

    Article  PubMed  Google Scholar 

  • Kakarala M, Brenner DE, Korkaya H, Cheng C, Tazi K, Ginestier C, Liu S, Dontu G, Wicha MS (2010) Targeting breast stem cells with the cancer preventive compounds curcumin and piperine. Breast Cancer Res Treat 122:777–785

    Article  CAS  PubMed  Google Scholar 

  • Kaldis P (2007) Another piece of the p27Kip1 puzzle. Cell 128:241–244

    Article  CAS  PubMed  Google Scholar 

  • Kamat AM, Sethi G, Aggarwal BB (2007) Curcumin potentiates the apoptotic effects of chemotherapeutic agents and cytokines through down-regulation of nuclear factor-kappaB and nuclear factor-kappaB-regulated gene products in IFN-alpha-sensitive and IFN-alpha-resistant human bladder cancer cells. Mol Cancer Ther 6:1022–1030

    Article  CAS  PubMed  Google Scholar 

  • Kandasamy K, Srivastava RK (2002) Role of the phosphatidylinositol 3′-kinase/PTEN/Akt kinase pathway in tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in non-small cell lung cancer cells. Cancer Res 62:4929–4937

    CAS  PubMed  Google Scholar 

  • Kandasamy K, Srinivasula SM, Alnemri ES, Thompson CB, Korsmeyer SJ, Bryant JL, Srivastava RK (2003) Involvement of proapoptotic molecules Bax and Bak in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced mitochondrial disruption and apoptosis: differential regulation of cytochrome c and Smac/DIABLO release. Cancer Res 63:1712–1721

    CAS  PubMed  Google Scholar 

  • Kanwar SS, Yu Y, Nautiyal J, Patel BB, Padhye S, Sarkar FH, Majumdar AP (2011) Difluorinated-curcumin (CDF): a novel curcumin analog is a potent inhibitor of colon cancer stem-like cells. Pharm Res 28:827–838

    Article  CAS  PubMed  Google Scholar 

  • Kardinal C, Dangers M, Kardinal A, Koch A, Brandt DT, Tamura T, Welte K (2006) Tyrosine phosphorylation modulates binding preference to cyclin-dependent kinases and subcellular localization of p27Kip1 in the acute promyelocytic leukemia cell line NB4. Blood 107:1133–1140

    Article  CAS  PubMed  Google Scholar 

  • Karin M (2006a) NF-kappaB and cancer: mechanisms and targets. Mol Carcinog 45:355–361

    Article  CAS  PubMed  Google Scholar 

  • Karin M (2006b) Nuclear factor-kappaB in cancer development and progression. Nature 441:431–436

    Article  CAS  PubMed  Google Scholar 

  • Kasperczyk H, Baumann B, Debatin KM, Fulda S (2009) Characterization of sonic hedgehog as a novel NF-kappaB target gene that promotes NF-kappaB-mediated apoptosis resistance and tumor growth in vivo. FASEB J 23:21–33

    Article  CAS  PubMed  Google Scholar 

  • Katoh Y, Katoh M (2009) Hedgehog target genes: mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation. Curr Mol Med 9:873–886

    Article  CAS  PubMed  Google Scholar 

  • Katz M, Amit I, Yarden Y (2007) Regulation of MAPKs by growth factors and receptor tyrosine kinases. Biochim Biophys Acta 1773:1161–1176

    Article  CAS  PubMed  Google Scholar 

  • Kelleher FC (2011) Hedgehog signaling and therapeutics in pancreatic cancer. Carcinogenesis 32:445–451

    Article  CAS  PubMed  Google Scholar 

  • Keshet Y, Seger R (2010) The MAP kinase signaling cascades: a system of hundreds of components regulates a diverse array of physiological functions. Methods Mol Biol 661:3–38

    Article  CAS  PubMed  Google Scholar 

  • Kettunen E, Nissen AM, Ollikainen T, Taavitsainen M, Tapper J, Mattson K, Linnainmaa K, Knuutila S, El-Rifai W (2001) Gene expression profiling of malignant mesothelioma cell lines: cDNA array study. Int J Cancer 91:492–496

    Article  CAS  PubMed  Google Scholar 

  • Keyomarsi K, Conte D Jr, Toyofuku W, Fox MP (1995) Deregulation of cyclin E in breast cancer. Oncogene 11:941–950

    CAS  PubMed  Google Scholar 

  • Keyomarsi K, Tucker SL, Buchholz TA, Callister M, Ding Y, Hortobagyi GN, Bedrosian I, Knickerbocker C, Toyofuku W, Lowe M, Herliczek TW, Bacus SS (2002) Cyclin E and survival in patients with breast cancer. N Engl J Med 347:1566–1575

    Article  CAS  PubMed  Google Scholar 

  • Khor TO, Keum YS, Lin W, Kim JH, Hu R, Shen G, Xu C, Gopalakrishnan A, Reddy B, Zheng X, Conney AH, Kong AN (2006) Combined inhibitory effects of curcumin and phenethyl isothiocyanate on the growth of human PC-3 prostate xenografts in immunodeficient mice. Cancer Res 66:613–621

    Article  CAS  PubMed  Google Scholar 

  • Khwaja A (1999) Akt is more than just a Bad kinase. Nature 401:33–34

    Article  CAS  PubMed  Google Scholar 

  • Kim JH, Kang MJ, Park CU, Kwak HJ, Hwang Y, Koh GY (1999) Amplified CDK2 and cdc2 activities in primary colorectal carcinoma. Cancer 85:546–553

    Article  CAS  PubMed  Google Scholar 

  • Kim H, Park BS, Lee KG, Choi CY, Jang SS, Kim YH, Lee SE (2005) Effects of naturally occurring compounds on fibril formation and oxidative stress of beta-amyloid. J Agric Food Chem 53:8537–8541

    Article  CAS  PubMed  Google Scholar 

  • Kim JH, Xu C, Keum YS, Reddy B, Conney A, Kong AN (2006) Inhibition of EGFR signaling in human prostate cancer PC-3 cells by combination treatment with beta-phenylethyl isothiocyanate and curcumin. Carcinogenesis 27:475–482

    Article  CAS  PubMed  Google Scholar 

  • Kitagawa M, Higashi H, Jung HK, Suzuki-Takahashi I, Ikeda M, Tamai K, Kato J, Segawa K, Yoshida E, Nishimura S, Taya Y (1996) The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2. EMBO J 15:7060–7069

    CAS  PubMed  Google Scholar 

  • Kitahara K, Yasui W, Kuniyasu H, Yokozaki H, Akama Y, Yunotani S, Hisatsugu T, Tahara E (1995) Concurrent amplification of cyclin E and CDK2 genes in colorectal carcinomas. Int J Cancer 62:25–28

    Article  CAS  PubMed  Google Scholar 

  • Klarmann GJ, Hurt EM, Mathews LA, Zhang X, Duhagon MA, Mistree T, Thomas SB, Farrar WL (2009) Invasive prostate cancer cells are tumor initiating cells that have a stem cell-like genomic signature. Clin Exp Metastasis 26:433–446

    Article  CAS  PubMed  Google Scholar 

  • Knudsen KE, Booth D, Naderi S, Sever-Chroneos Z, Fribourg AF, Hunton IC, Feramisco JR, Wang JY, Knudsen ES (2000) RB-dependent S-phase response to DNA damage. Mol Cell Biol 20:7751–7763

    Article  CAS  PubMed  Google Scholar 

  • Koff A (2006) How to decrease p27Kip1 levels during tumor development. Cancer Cell 9:75–76

    Article  CAS  PubMed  Google Scholar 

  • Kopan R, Ilagan MX (2009) The canonical Notch signaling pathway: unfolding the activation mechanism. Cell 137:216–233

    Article  CAS  PubMed  Google Scholar 

  • Korkaya H, Paulson A, Charafe-Jauffret E, Ginestier C, Brown M, Dutcher J, Clouthier SG, Wicha MS (2009) Regulation of mammary stem/progenitor cells by PTEN/Akt/beta-catenin signaling. PLoS Biol 7:e1000121

    Article  PubMed  CAS  Google Scholar 

  • Korutla L, Kumar R (1994) Inhibitory effect of curcumin on epidermal growth factor receptor kinase activity in A431 cells. Biochim Biophys Acta 1224:597–600

    Article  PubMed  Google Scholar 

  • Korutla L, Cheung JY, Mendelsohn J, Kumar R (1995) Inhibition of ligand-induced activation of epidermal growth factor receptor tyrosine phosphorylation by curcumin. Carcinogenesis 16:1741–1745

    Article  CAS  PubMed  Google Scholar 

  • Kunnumakkara AB, Guha S, Krishnan S, Diagaradjane P, Gelovani J, Aggarwal BB (2007) Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res 67:3853–3861

    Article  CAS  PubMed  Google Scholar 

  • Kunnumakkara AB, Anand P, Aggarwal BB (2008) Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett 269:199–225

    Article  CAS  PubMed  Google Scholar 

  • Kuwana T, Newmeyer DD (2003) Bcl-2-family proteins and the role of mitochondria in apoptosis. Curr Opin Cell Biol 15:691–699

    Article  CAS  PubMed  Google Scholar 

  • Lawlor MA, Alessi DR (2001) PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? J Cell Sci 114:2903–2910

    CAS  PubMed  Google Scholar 

  • Leach FS, Elledge SJ, Sherr CJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B (1993) Amplification of cyclin genes in colorectal carcinomas. Cancer Res 53:1986–1989

    CAS  PubMed  Google Scholar 

  • Lee JY, Lee YM, Chang GC, Yu SL, Hsieh WY, Chen JJ, Chen HW, Yang PC (2011) Curcumin induces EGFR degradation in lung adenocarcinoma and modulates p38 activation in intestine: the versatile adjuvant for gefitinib therapy. PLoS One 6:e23756

    Article  CAS  PubMed  Google Scholar 

  • Lees E (1995) Cyclin dependent kinase regulation. Curr Opin Cell Biol 7:773–780

    Article  CAS  PubMed  Google Scholar 

  • Lei H, Furlong PJ, Ra JH, Mullins D, Cantor R, Fraker DL, Spitz FR (2005) AKT activation and response to interferon-beta in human cancer cells. Cancer Biol Ther 4:709–715

    Article  CAS  PubMed  Google Scholar 

  • Lentzsch S, Chatterjee M, Gries M, Bommert K, Gollasch H, Dorken B, Bargou RC (2004) PI3-K/AKT/FKHR and MAPK signaling cascades are redundantly stimulated by a variety of cytokines and contribute independently to proliferation and survival of multiple myeloma cells. Leukemia 18:1883–1890

    Article  CAS  PubMed  Google Scholar 

  • Lev-Ari S, Starr A, Vexler A, Karaush V, Loew V, Greif J, Fenig E, Aderka D, Ben-Yosef R (2006) Inhibition of pancreatic and lung adenocarcinoma cell survival by curcumin is associated with increased apoptosis, down-regulation of COX-2 and EGFR and inhibition of Erk1/2 activity. Anticancer Res 26:4423–4430

    CAS  PubMed  Google Scholar 

  • Lew DJ, Kornbluth S (1996) Regulatory roles of cyclin dependent kinase phosphorylation in cell cycle control. Curr Opin Cell Biol 8:795–804

    Article  CAS  PubMed  Google Scholar 

  • Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R (1997) PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275:1943–1947

    Article  CAS  PubMed  Google Scholar 

  • Li M, Zhang Z, Hill DL, Wang H, Zhang R (2007) Curcumin, a dietary component, has anticancer, chemosensitization, and radiosensitization effects by down-regulating the MDM2 oncogene through the PI3K/mTOR/ETS2 pathway. Cancer Res 67:1988–1996

    Article  CAS  PubMed  Google Scholar 

  • Li T, Wang W, Chen H, Ye L (2010) Evaluation of anti-leukemia effect of resveratrol by modulating STAT3 signaling. Int Immunopharmacol 10:18–25

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Wicha MS, Schwartz SJ, Sun D (2011) Implications of cancer stem cell theory for cancer chemoprevention by natural dietary compounds. J Nutr Biochem 22(9):799–806

    Article  CAS  PubMed  Google Scholar 

  • Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM (2001) The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 21:8370–8377

    CAS  PubMed  Google Scholar 

  • Lin J, Chen A (2011) Curcumin diminishes the impacts of hyperglycemia on the activation of hepatic stellate cells by suppressing membrane translocation and gene expression of glucose transporter-2. Mol Cell Endocrinol 333:160–171

    Article  CAS  PubMed  Google Scholar 

  • Lin SY, Xia W, Wang JC, Kwong KY, Spohn B, Wen Y, Pestell RG, Hung MC (2000) Beta-catenin, a novel prognostic marker for breast cancer: its roles in cyclin D1 expression and cancer progression. Proc Natl Acad Sci U S A 97:4262–4266

    Article  CAS  PubMed  Google Scholar 

  • Lin SK, Kok SH, Yeh FT, Kuo MY, Lin CC, Wang CC, Goldring SR, Hong CY (2004) MEK/ERK and signal transducer and activator of transcription signaling pathways modulate oncostatin M-stimulated CCL2 expression in human osteoblasts through a common transcription factor. Arthritis Rheum 50:785–793

    Article  CAS  PubMed  Google Scholar 

  • Lin YG, Kunnumakkara AB, Nair A, Merritt WM, Han LY, Armaiz-Pena GN, Kamat AA, Spannuth WA, Gershenson DM, Lutgendorf SK, Aggarwal BB, Sood AK (2007) Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-kappaB pathway. Clin Cancer Res 13:3423–3430

    Article  CAS  PubMed  Google Scholar 

  • Lin L, Deangelis S, Foust E, Fuchs J, Li C, Li PK, Schwartz EB, Lesinski GB, Benson D, Lu J, Hoyt D, Lin J (2010a) A novel small molecule inhibits STAT3 phosphorylation and DNA binding activity and exhibits potent growth suppressive activity in human cancer cells. Mol Cancer 9:217

    Article  CAS  PubMed  Google Scholar 

  • Lin L, Hutzen B, Zuo M, Ball S, Deangelis S, Foust E, Pandit B, Ihnat MA, Shenoy SS, Kulp S, Li PK, Li C, Fuchs J, Lin J (2010b) Novel STAT3 phosphorylation inhibitors exhibit potent growth-suppressive activity in pancreatic and breast cancer cells. Cancer Res 70:2445–2454

    Article  CAS  PubMed  Google Scholar 

  • Lindner V, Booth C, Prudovsky I, Small D, Maciag T, Liaw L (2001) Members of the Jagged/Notch gene families are expressed in injured arteries and regulate cell phenotype via alterations in cell matrix and cell-cell interaction. Am J Pathol 159:875–883

    Article  CAS  PubMed  Google Scholar 

  • Lindsten T, Ross AJ, King A, Zong WX, Rathmell JC, Shiels HA, Ulrich E, Waymire KG, Mahar P, Frauwirth K, Chen Y, Wei M, Eng VM, Adelman DM, Simon MC, Ma A, Golden JA, Evan G, Korsmeyer SJ, MacGregor GR, Thompson CB (2000) The combined functions of proapoptotic Bcl-2 family members Bak and Bax are essential for normal development of multiple tissues. Mol Cell 6:1389–1399

    Article  CAS  PubMed  Google Scholar 

  • Ling H, Sylvestre JR, Jolicoeur P (2010) Notch1-induced mammary tumor development is cyclin D1-dependent and correlates with expansion of pre-malignant multipotent duct-limited progenitors. Oncogene 29:4543–4554

    Article  CAS  PubMed  Google Scholar 

  • Liu ZG, Hsu H, Goeddel DV, Karin M (1996) Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-kappaB activation prevents cell death. Cell 87:565–576

    Article  CAS  PubMed  Google Scholar 

  • Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, He X (2002) Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108:837–847

    Article  CAS  PubMed  Google Scholar 

  • Liu S, Dontu G, Wicha MS (2005) Mammary stem cells, self-renewal pathways, and carcinogenesis. Breast Cancer Res 7:86–95

    Article  CAS  PubMed  Google Scholar 

  • Liu S, Dontu G, Mantle ID, Patel S, Ahn NS, Jackson KW, Suri P, Wicha MS (2006) Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res 66:6063–6071

    Article  CAS  PubMed  Google Scholar 

  • Liu S, Ma Z, Cai H, Li Q, Rong W, Kawano M (2010) Inhibitory effect of baicalein on IL-6-mediated signaling cascades in human myeloma cells. Eur J Haematol 84:137–144

    Article  CAS  PubMed  Google Scholar 

  • Lo HW (2010) EGFR-targeted therapy in malignant glioma: novel aspects and mechanisms of drug resistance. Curr Mol Pharmacol 3:37–52

    CAS  PubMed  Google Scholar 

  • Loda M, Cukor B, Tam SW, Lavin P, Fiorentino M, Draetta GF, Jessup JM, Pagano M (1997) Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat Med 3:231–234

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Otin C, Matrisian LM (2007) Emerging roles of proteases in tumour suppression. Nat Rev Cancer 7:800–808

    Article  CAS  PubMed  Google Scholar 

  • Lu CD, Morita S, Ishibashi T, Hara H, Isozaki H, Tanigawa N (1999) Loss of p27Kip1 expression independently predicts poor prognosis for patients with resectable pancreatic adenocarcinoma. Cancer 85:1250–1260

    Article  CAS  PubMed  Google Scholar 

  • Ludlow JW, Glendening CL, Livingston DM, DeCarprio JA (1993) Specific enzymatic dephosphorylation of the retinoblastoma protein. Mol Cell Biol 13:367–372

    CAS  PubMed  Google Scholar 

  • Luo J, Manning BD, Cantley LC (2003) Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell 4:257–262

    Article  CAS  PubMed  Google Scholar 

  • Lynch CC (2011) Matrix metalloproteinases as master regulators of the vicious cycle of bone metastasis. Bone 48:44–53

    Article  CAS  PubMed  Google Scholar 

  • MacFarlane M, Merrison W, Bratton SB, Cohen GM (2002) Proteasome-mediated degradation of Smac during apoptosis: XIAP promotes Smac ubiquitination in vitro. J Biol Chem 277:36611–36616

    Article  CAS  PubMed  Google Scholar 

  • Madoux F, Koenig M, Sessions H, Nelson E, Mercer BA, Cameron M, Roush W, Frank D, Hodder P (2010) Modulators of STAT transcription factors for the targeted therapy of cancer (STAT3 inhibitors)

    Google Scholar 

  • Maehama T, Dixon JE (1999) PTEN: a tumour suppressor that functions as a phospholipid phosphatase. Trends Cell Biol 9:125–128

    Article  CAS  PubMed  Google Scholar 

  • Maheshwari RK, Singh AK, Gaddipati J, Srimal RC (2006) Multiple biological activities of curcumin: a short review. Life Sci 78:2081–2087

    Article  CAS  PubMed  Google Scholar 

  • Mani H, Sidhu GS, Kumari R, Gaddipati JP, Seth P, Maheshwari RK (2002) Curcumin differentially regulates TGF-beta1, its receptors and nitric oxide synthase during impaired wound healing. Biofactors 16:29–43

    Article  CAS  PubMed  Google Scholar 

  • Mann B, Gelos M, Siedow A, Hanski ML, Gratchev A, Ilyas M, Bodmer WF, Moyer MP, Riecken EO, Buhr HJ, Hanski C (1999) Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas. Proc Natl Acad Sci U S A 96:1603–1608

    Article  CAS  PubMed  Google Scholar 

  • Manoharan S, Balakrishnan S, Menon VP, Alias LM, Reena AR (2009) Chemopreventive efficacy of curcumin and piperine during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Singapore Med J 50:139–146

    CAS  PubMed  Google Scholar 

  • Martinez AM, Cavalli G (2010) Uncovering a tumor-suppressor function for Drosophila polycomb group genes. Cell Cycle 9:215–216

    Article  CAS  PubMed  Google Scholar 

  • Martinez AM, Schuettengruber B, Sakr S, Janic A, Gonzalez C, Cavalli G (2009) Polyhomeotic has a tumor suppressor activity mediated by repression of Notch signaling. Nat Genet 41:1076–1082

    Article  CAS  PubMed  Google Scholar 

  • Mazumdar J, Dondeti V, Simon MC (2009) Hypoxia-inducible factors in stem cells and cancer. J Cell Mol Med 13:4319–4328

    Article  CAS  PubMed  Google Scholar 

  • McDonald ER 3rd, El-Deiry WS (2000) Cell cycle control as a basis for cancer drug development (review). Int J Oncol 16:871–886

    CAS  PubMed  Google Scholar 

  • Merchant AA, Matsui W (2010) Targeting Hedgehog–a cancer stem cell pathway. Clin Cancer Res 16:3130–3140

    Article  CAS  PubMed  Google Scholar 

  • Michl P, Downward J (2005) Mechanisms of disease: PI3K/AKT signaling in gastrointestinal cancers. Z Gastroenterol 43:1133–1139

    Article  CAS  PubMed  Google Scholar 

  • Miele L (2006) Notch signaling. Clin Cancer Res 12:1074–1079

    Article  CAS  PubMed  Google Scholar 

  • Miele L, Golde T, Osborne B (2006) Notch signaling in cancer. Curr Mol Med 6:905–918

    Article  CAS  PubMed  Google Scholar 

  • Migita T, Oda Y, Naito S, Tsuneyoshi M (2002) Low expression of p27(Kip1) is associated with tumor size and poor prognosis in patients with renal cell carcinoma. Cancer 94:973–979

    Article  CAS  PubMed  Google Scholar 

  • Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P, Moll UM (2003) p53 has a direct apoptogenic role at the mitochondria. Mol Cell 11:577–590

    Article  CAS  PubMed  Google Scholar 

  • Millard SS, Yan JS, Nguyen H, Pagano M, Kiyokawa H, Koff A (1997) Enhanced ribosomal association of p27(Kip1) mRNA is a mechanism contributing to accumulation during growth arrest. J Biol Chem 272:7093–7098

    Article  CAS  PubMed  Google Scholar 

  • Mimeault M, Batra SK (2011) Potential applications of curcumin and its novel synthetic analogs and nanotechnology-based formulations in cancer prevention and therapy. Chin Med 6:31

    Article  CAS  PubMed  Google Scholar 

  • Min L, He B, Hui L (2011) Mitogen-activated protein kinases in hepatocellular carcinoma development. Semin Cancer Biol 21:10–20

    Article  CAS  PubMed  Google Scholar 

  • Mineta H, Miura K, Suzuki I, Takebayashi S, Misawa K, Ueda Y, Ichimura K (1999) p27 expression correlates with prognosis in patients with hypopharyngeal cancer. Anticancer Res 19:4407–4412

    CAS  PubMed  Google Scholar 

  • Morgan DO (1995) Principles of CDK regulation. Nature 374:131–134

    Article  CAS  PubMed  Google Scholar 

  • Motokura T, Bloom T, Kim HG, Juppner H, Ruderman JV, Kronenberg HM, Arnold A (1991) A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature 350:512–515

    Article  CAS  PubMed  Google Scholar 

  • Muller-Tidow C, Metzger R, Kugler K, Diederichs S, Idos G, Thomas M, Dockhorn-Dworniczak B, Schneider PM, Koeffler HP, Berdel WE, Serve H (2001) Cyclin E is the only cyclin-dependent kinase 2-associated cyclin that predicts metastasis and survival in early stage non-small cell lung cancer. Cancer Res 61:647–653

    CAS  PubMed  Google Scholar 

  • Myers MP, Pass I, Batty IH, Van der Kaay J, Stolarov JP, Hemmings BA, Wigler MH, Downes CP, Tonks NK (1998) The lipid phosphatase activity of PTEN is critical for its tumor suppressor function. Proc Natl Acad Sci U S A 95:13513–13518

    Article  CAS  PubMed  Google Scholar 

  • Nakashima H, Nakamura M, Yamaguchi H, Yamanaka N, Akiyoshi T, Koga K, Yamaguchi K, Tsuneyoshi M, Tanaka M, Katano M (2006) Nuclear factor-kappaB contributes to Hedgehog signaling pathway activation through sonic hedgehog induction in pancreatic cancer. Cancer Res 66:7041–7049

    Article  CAS  PubMed  Google Scholar 

  • Natsume A, Kinjo S, Yuki K, Kato T, Ohno M, Motomura K, Iwami K, Wakabayashi T (2011) Glioma-initiating cells and molecular pathology: implications for therapy. Brain Tumor Pathol 28:1–12

    Article  CAS  PubMed  Google Scholar 

  • Nelson WJ, Nusse R (2004) Convergence of Wnt, beta-catenin, and cadherin pathways. Science 303:1483–1487

    Article  CAS  PubMed  Google Scholar 

  • Nevins JR, Leone G, DeGregori J, Jakoi L (1997) Role of the Rb/E2F pathway in cell growth control. J Cell Physiol 173:233–236

    Article  CAS  PubMed  Google Scholar 

  • Nickoloff BJ, Qin JZ, Chaturvedi V, Denning MF, Bonish B, Miele L (2002) Jagged-1 mediated activation of notch signaling induces complete maturation of human keratinocytes through NF-kappaB and PPARgamma. Cell Death Differ 9:842–855

    Article  CAS  PubMed  Google Scholar 

  • Nirmala C, Puvanakrishnan R (1996a) Effect of curcumin on certain lysosomal hydrolases in isoproterenol-induced myocardial infarction in rats. Biochem Pharmacol 51:47–51

    Article  CAS  PubMed  Google Scholar 

  • Nirmala C, Puvanakrishnan R (1996b) Protective role of curcumin against isoproterenol induced myocardial infarction in rats. Mol Cell Biochem 159:85–93

    Article  CAS  PubMed  Google Scholar 

  • Noseda M, McLean G, Niessen K, Chang L, Pollet I, Montpetit R, Shahidi R, Dorovini-Zis K, Li L, Beckstead B, Durand RE, Hoodless PA, Karsan A (2004) Notch activation results in phenotypic and functional changes consistent with endothelial-to-mesenchymal transformation. Circ Res 94:910–917

    Article  CAS  PubMed  Google Scholar 

  • Nowak MA, Komarova NL, Sengupta A, Jallepalli PV, Shih Ie M, Vogelstein B, Lengauer C (2002) The role of chromosomal instability in tumor initiation. Proc Natl Acad Sci U S A 99:16226–16231

    Article  CAS  PubMed  Google Scholar 

  • Oakes SA, Scorrano L, Opferman JT, Bassik MC, Nishino M, Pozzan T, Korsmeyer SJ (2005) Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum. Proc Natl Acad Sci U S A 102:105–110

    Article  CAS  PubMed  Google Scholar 

  • Ohtsubo M, Theodoras AM, Schumacher J, Roberts JM, Pagano M (1995) Human cyclin E, a nuclear protein essential for the G1-to-S phase transition. Mol Cell Biol 15:2612–2624

    CAS  PubMed  Google Scholar 

  • Okuhashi Y, Nara N, Tohda S (2010) Effects of gamma-secretase inhibitors on the growth of leukemia cells. Anticancer Res 30:495–498

    CAS  PubMed  Google Scholar 

  • Okunieff P, Xu J, Hu D, Liu W, Zhang L, Morrow G, Pentland A, Ryan JL, Ding I (2006) Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines. Int J Radiat Oncol Biol Phys 65:890–898

    Article  CAS  PubMed  Google Scholar 

  • Ophascharoensuk V, Fero ML, Hughes J, Roberts JM, Shankland SJ (1998) The cyclin-dependent kinase inhibitor p27Kip1 safeguards against inflammatory injury. Nat Med 4:575–580

    Article  CAS  PubMed  Google Scholar 

  • Ortega S, Malumbres M, Barbacid M (2002) Cyclin D-dependent kinases, INK4 inhibitors and cancer. Biochim Biophys Acta 1602:73–87

    CAS  PubMed  Google Scholar 

  • Oswald F, Liptay S, Adler G, Schmid RM (1998) NF-kappaB2 is a putative target gene of activated Notch-1 via RBP-Jkappa. Mol Cell Biol 18:2077–2088

    CAS  PubMed  Google Scholar 

  • Palomero T, Sulis ML, Cortina M, Real PJ, Barnes K, Ciofani M, Caparros E, Buteau J, Brown K, Perkins SL, Bhagat G, Agarwal AM, Basso G, Castillo M, Nagase S, Cordon-Cardo C, Parsons R, Zuniga-Pflucker JC, Dominguez M, Ferrando AA (2007) Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nat Med 13:1203–1210

    Article  CAS  PubMed  Google Scholar 

  • Pandey MK, Sung B, Aggarwal BB (2010) Betulinic acid suppresses STAT3 activation pathway through induction of protein tyrosine phosphatase SHP-1 in human multiple myeloma cells. Int J Cancer 127:282–292

    CAS  PubMed  Google Scholar 

  • Pang RT, Leung CO, Ye TM, Liu W, Chiu PC, Lam KK, Lee KF, Yeung WS (2010) MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells. Carcinogenesis 31:1037–1044

    Article  CAS  PubMed  Google Scholar 

  • Pap M, Cooper GM (1998) Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-Kinase/Akt cell survival pathway. J Biol Chem 273:19929–19932

    Article  CAS  PubMed  Google Scholar 

  • Park CH, Hahm ER, Park S, Kim HK, Yang CH (2005) The inhibitory mechanism of curcumin and its derivative against beta-catenin/Tcf signaling. FEBS Lett 579:2965–2971

    Article  CAS  PubMed  Google Scholar 

  • Parodi FE, Mao D, Ennis TL, Pagano MB, Thompson RW (2006) Oral administration of diferuloylmethane (curcumin) suppresses proinflammatory cytokines and destructive connective tissue remodeling in experimental abdominal aortic aneurysms. Ann Vasc Surg 20:360–368

    Article  PubMed  Google Scholar 

  • Pasca di Magliano M, Hebrok M (2003) Hedgehog signalling in cancer formation and maintenance. Nat Rev Cancer 3:903–911

    Article  PubMed  Google Scholar 

  • Paulovich AG, Hartwell LH (1995) A checkpoint regulates the rate of progression through S phase in S. cerevisiae in response to DNA damage. Cell 82:841–847

    Article  CAS  PubMed  Google Scholar 

  • Peant B, Diallo JS, Lessard L, Delvoye N, Le Page C, Saad F, Mes-Masson AM (2007) Regulation of IkappaB kinase epsilon expression by the androgen receptor and the nuclear factor-kappaB transcription factor in prostate cancer. Mol Cancer Res 5:87–94

    Article  CAS  PubMed  Google Scholar 

  • Pece S, Confalonieri S, Romano PR, Di Fiore PP (2011) NUMB-ing down cancer by more than just a NOTCH. Biochim Biophys Acta 1815:26–43

    CAS  PubMed  Google Scholar 

  • Pines J (1995) Cyclins, CDKs and cancer. Semin Cancer Biol 6:63–72

    Article  CAS  PubMed  Google Scholar 

  • Piper JT, Singhal SS, Salameh MS, Torman RT, Awasthi YC, Awasthi S (1998) Mechanisms of anticarcinogenic properties of curcumin: the effect of curcumin on glutathione linked detoxification enzymes in rat liver. Int J Biochem Cell Biol 30:445–456

    Article  CAS  PubMed  Google Scholar 

  • Plummer SM, Holloway KA, Manson MM, Munks RJ, Kaptein A, Farrow S, Howells L (1999) Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signalling complex. Oncogene 18:6013–6020

    Article  CAS  PubMed  Google Scholar 

  • Plummer SM, Hill KA, Festing MF, Steward WP, Gescher AJ, Sharma RA (2001) Clinical development of leukocyte cyclooxygenase 2 activity as a systemic biomarker for cancer chemopreventive agents. Cancer Epidemiol Biomarkers Prev 10:1295–1299

    CAS  PubMed  Google Scholar 

  • Polakis P (2000) Wnt signaling and cancer. Genes Dev 14:1837–1851

    CAS  PubMed  Google Scholar 

  • Polytarchou C, Hatziapostolou M, Papadimitriou E (2005) Hydrogen peroxide stimulates proliferation and migration of human prostate cancer cells through activation of activator protein-1 and up-regulation of the heparin affin regulatory peptide gene. J Biol Chem 280:40428–40435

    Article  CAS  PubMed  Google Scholar 

  • Ponce-Castaneda MV, Lee MH, Latres E, Polyak K, Lacombe L, Montgomery K, Mathew S, Krauter K, Sheinfeld J, Massague J et al (1995) p27Kip1: chromosomal mapping to 12p12-12p13.1 and absence of mutations in human tumors. Cancer Res 55:1211–1214

    CAS  PubMed  Google Scholar 

  • Porter PL, Malone KE, Heagerty PJ, Alexander GM, Gatti LA, Firpo EJ, Daling JR, Roberts JM (1997) Expression of cell-cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients. Nat Med 3:222–225

    Article  CAS  PubMed  Google Scholar 

  • Radtke F, Fasnacht N, Macdonald HR (2010) Notch signaling in the immune system. Immunity 32:14–27

    Article  CAS  PubMed  Google Scholar 

  • Raffo D, Pontiggia O, Simian M (2011) Role of MMPs in metastatic dissemination: implications for therapeutic advances. Curr Pharm Biotechnol

    Google Scholar 

  • Rajasingh J, Raikwar HP, Muthian G, Johnson C, Bright JJ (2006) Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia. Biochem Biophys Res Commun 340:359–368

    Article  CAS  PubMed  Google Scholar 

  • Ramakrishnan V, Kimlinger T, Haug J, Timm M, Wellik L, Halling T, Pardanani A, Tefferi A, Rajkumar SV, Kumar S (2010) TG101209, a novel JAK2 inhibitor, has significant in vitro activity in multiple myeloma and displays preferential cytotoxicity for CD45+ myeloma cells. Am J Hematol 85:675–686

    Article  CAS  PubMed  Google Scholar 

  • Ramirez Bosca A, Soler A, Carrion-Gutierrez MA, Pamies Mira D, Pardo Zapata J, Diaz-Alperi J, Bernd A, Quintanilla Almagro E, Miquel J (2000) An hydroalcoholic extract of Curcuma longa lowers the abnormally high values of human-plasma fibrinogen. Mech Ageing Dev 114:207–210

    Article  CAS  PubMed  Google Scholar 

  • Reddy AC, Lokesh BR (1992) Studies on spice principles as antioxidants in the inhibition of lipid peroxidation of rat liver microsomes. Mol Cell Biochem 111:117–124

    CAS  PubMed  Google Scholar 

  • Reddy AC, Lokesh BR (1994) Effect of dietary turmeric (Curcuma longa) on iron-induced lipid peroxidation in the rat liver. Food Chem Toxicol 32:279–283

    Article  CAS  PubMed  Google Scholar 

  • Rezende LF, Vieira AS, Negro A, Langone F, Boschero AC (2009) Ciliary neurotrophic factor (CNTF) signals through STAT3-SOCS3 pathway and protects rat pancreatic islets from cytokine-induced apoptosis. Cytokine 46:65–71

    Article  CAS  PubMed  Google Scholar 

  • Ronchini C, Capobianco AJ (2001) Induction of cyclin D1 transcription and CDK2 activity by Notch(ic): implication for cell cycle disruption in transformation by Notch(ic). Mol Cell Biol 21:5925–5934

    Article  CAS  PubMed  Google Scholar 

  • Rosen DG, Yang G, Deavers MT, Malpica A, Kavanagh JJ, Mills GB, Liu J (2006) Cyclin E expression is correlated with tumor progression and predicts a poor prognosis in patients with ovarian carcinoma. Cancer 106:1925–1932

    Article  CAS  PubMed  Google Scholar 

  • Rushworth SA, Ogborne RM, Charalambos CA, O’Connell MA (2006) Role of protein kinase C delta in curcumin-induced antioxidant response element-mediated gene expression in human monocytes. Biochem Biophys Res Commun 341:1007–1016

    Article  CAS  PubMed  Google Scholar 

  • Ryu MJ, Cho M, Song JY, Yun YS, Choi IW, Kim DE, Park BS, Oh S (2008) Natural derivatives of curcumin attenuate the Wnt/beta-catenin pathway through down-regulation of the transcriptional coactivator p300. Biochem Biophys Res Commun 377:1304–1308

    Article  CAS  PubMed  Google Scholar 

  • Salh B, Assi K, Templeman V, Parhar K, Owen D, Gomez-Munoz A, Jacobson K (2003) Curcumin attenuates DNB-induced murine colitis. Am J Physiol Gastrointest Liver Physiol 285:G235–G243

    CAS  PubMed  Google Scholar 

  • Sandur SK, Pandey MK, Sung B, Aggarwal BB (2010) 5-hydroxy-2-methyl-1,4-naphthoquinone, a vitamin K3 analogue, suppresses STAT3 activation pathway through induction of protein tyrosine phosphatase, SHP-1: potential role in chemosensitization. Mol Cancer Res 8:107–118

    Article  CAS  PubMed  Google Scholar 

  • Santagata S, Demichelis F, Riva A, Varambally S, Hofer MD, Kutok JL, Kim R, Tang J, Montie JE, Chinnaiyan AM, Rubin MA, Aster JC (2004) JAGGED1 expression is associated with prostate cancer metastasis and recurrence. Cancer Res 64:6854–6857

    Article  CAS  PubMed  Google Scholar 

  • Sarkar FH, Li Y, Wang Z, Kong D (2009) Cellular signaling perturbation by natural products. Cell Signal 21:1541–1547

    Article  CAS  PubMed  Google Scholar 

  • Sarkar FH, Li Y, Wang Z, Kong D (2010) Novel targets for prostate cancer chemoprevention. Endocr Relat Cancer 17:R195–R212

    Article  CAS  PubMed  Google Scholar 

  • Schmidt M, Fernandez de Mattos S, van der Horst A, Klompmaker R, Kops GJ, Lam EW, Burgering BM, Medema RH (2002) Cell cycle inhibition by FoxO forkhead transcription factors involves downregulation of cyclin D. Mol Cell Biol 22:7842–7852

    Article  CAS  PubMed  Google Scholar 

  • Schweizer L, Varmus H (2003) Wnt/Wingless signaling through beta-catenin requires the function of both LRP/Arrow and frizzled classes of receptors. BMC Cell Biol 4:4

    Article  PubMed  Google Scholar 

  • Scorrano L, Korsmeyer SJ (2003) Mechanisms of cytochrome c release by proapoptotic BCL-2 family members. Biochem Biophys Res Commun 304:437–444

    Article  CAS  PubMed  Google Scholar 

  • Scuderi R, Palucka KA, Pokrovskaja K, Bjorkholm M, Wiman KG, Pisa P (1996) Cyclin E overexpression in relapsed adult acute lymphoblastic leukemias of B-cell lineage. Blood 87:3360–3367

    CAS  PubMed  Google Scholar 

  • Scuto A, Krejci P, Popplewell L, Wu J, Wang Y, Kujawski M, Kowolik C, Xin H, Chen L, Kretzner L, Yu H, Wilcox WR, Yen Y, Forman S, Jove R (2011) The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting in suppression of human myeloma cell growth and survival. Leukemia 25:538–550

    Article  CAS  PubMed  Google Scholar 

  • Seo JH, Jeong KJ, Oh WJ, Sul HJ, Sohn JS, Kim YK, Cho do Y, Kang JK, Park CG, Lee HY (2010) Lysophosphatidic acid induces STAT3 phosphorylation and ovarian cancer cell motility: their inhibition by curcumin. Cancer Lett 288:50–56

    Article  CAS  PubMed  Google Scholar 

  • Shaikh J, Ankola DD, Beniwal V, Singh D, Kumar MN (2009) Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. Eur J Pharm Sci 37:223–230

    Article  CAS  PubMed  Google Scholar 

  • Shankar S, Srivastava RK (2004) Enhancement of therapeutic potential of TRAIL by cancer chemotherapy and irradiation: mechanisms and clinical implications. Drug Resist Updat 7:139–156

    Article  CAS  PubMed  Google Scholar 

  • Shankar S, Srivastava RK (2007a) Bax and Bak genes are essential for maximum apoptotic response by curcumin, a polyphenolic compound and cancer chemopreventive agent derived from turmeric, Curcuma longa. Carcinogenesis 28:1277–1286

    Article  CAS  PubMed  Google Scholar 

  • Shankar S, Srivastava RK (2007b) Involvement of Bcl-2 family members, phosphatidylinositol 3′-kinase/AKT and mitochondrial p53 in curcumin (diferulolylmethane)-induced apoptosis in prostate cancer. Int J Oncol 30:905–918

    CAS  PubMed  Google Scholar 

  • Shankar S, Singh TR, Srivastava RK (2004) Ionizing radiation enhances the therapeutic potential of TRAIL in prostate cancer in vitro and in vivo: intracellular mechanisms. Prostate 61:35–49

    Article  CAS  PubMed  Google Scholar 

  • Shankar S, Chen X, Srivastava RK (2005) Effects of sequential treatments with chemotherapeutic drugs followed by TRAIL on prostate cancer in vitro and in vivo. Prostate 62:165–186

    Article  CAS  PubMed  Google Scholar 

  • Shankar S, Chen Q, Sarva K, Siddiqui I, Srivastava RK (2007a) Curcumin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells: molecular mechanisms of apoptosis, migration and angiogenesis. J Mol Signal 2:10

    Article  PubMed  CAS  Google Scholar 

  • Shankar S, Chen Q, Siddiqui I, Sarva K, Srivastava RK (2007b) Sensitization of TRAIL-resistant LNCaP cells by resveratrol (3, 4′, 5 tri-hydroxystilbene): molecular mechanisms and therapeutic potential. J Mol Signal 2:7

    Article  PubMed  CAS  Google Scholar 

  • Shankar S, Qinghe C, Sidiqui I, Srivastava RK (2007c) Curcumin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells: molecular mechanisms of apoptosis, metastasis and angiogenesis. Cancer Res (In press)

    Google Scholar 

  • Shankar S, Ganapathy S, Chen Q, Srivastava RK (2008) Curcumin sensitizes TRAIL-resistant xenografts: molecular mechanisms of apoptosis, metastasis and angiogenesis. Mol Cancer 7:16

    Article  PubMed  CAS  Google Scholar 

  • Shanmugam MK, Kannaiyan R, Sethi G (2011) Targeting cell signaling and apoptotic pathways by dietary agents: role in the prevention and treatment of cancer. Nutr Cancer 63:161–173

    Article  CAS  PubMed  Google Scholar 

  • Sharma RA, Ireson CR, Verschoyle RD, Hill KA, Williams ML, Leuratti C, Manson MM, Marnett LJ, Steward WP, Gescher A (2001) Effects of dietary curcumin on glutathione S-transferase and malondialdehyde-DNA adducts in rat liver and colon mucosa: relationship with drug levels. Clin Cancer Res 7:1452–1458

    CAS  PubMed  Google Scholar 

  • Sharma S, Kulkarni SK, Agrewala JN, Chopra K (2006) Curcumin attenuates thermal hyperalgesia in a diabetic mouse model of neuropathic pain. Eur J Pharmacol 536:256–261

    Article  CAS  PubMed  Google Scholar 

  • Sharma VM, Draheim KM, Kelliher MA (2007) The Notch1/c-Myc pathway in T cell leukemia. Cell Cycle 6:927–930

    Article  CAS  PubMed  Google Scholar 

  • Sharma M, Manoharlal R, Puri N, Prasad R (2010) Antifungal curcumin induces reactive oxygen species and triggers an early apoptosis but prevents hyphae development by targeting the global repressor TUP1 in Candida albicans. Biosci Rep 30:391–404

    Article  CAS  PubMed  Google Scholar 

  • Sharmila Shankar QC, Siddiqui I, Srivastava RK (2007) Curcumin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells: molecular mechanisms of apoptosis, migration and angiogenesis. J Mol Signal 2:10

    Article  PubMed  CAS  Google Scholar 

  • Shenouda NS, Zhou C, Browning JD, Ansell PJ, Sakla MS, Lubahn DB, Macdonald RS (2004) Phytoestrogens in common herbs regulate prostate cancer cell growth in vitro. Nutr Cancer 49:200–208

    Article  CAS  PubMed  Google Scholar 

  • Sherr CJ (1994) G1 phase progression: cycling on cue. Cell 79:551–555

    Article  CAS  PubMed  Google Scholar 

  • Sherr CJ (1996) Cancer cell cycles. Science 274:1672–1677

    Article  CAS  PubMed  Google Scholar 

  • Sherr CJ (2002) D1 in G2. Cell Cycle 1:36–38

    Article  CAS  PubMed  Google Scholar 

  • Sherr CJ, Roberts JM (1995) Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev 9:1149–1163

    Article  CAS  PubMed  Google Scholar 

  • Sherr CJ, Roberts JM (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13:1501–1512

    Article  CAS  PubMed  Google Scholar 

  • Shin HM, Minter LM, Cho OH, Gottipati S, Fauq AH, Golde TE, Sonenshein GE, Osborne BA (2006) Notch1 augments NF-kappaB activity by facilitating its nuclear retention. EMBO J 25:129–138

    Article  CAS  PubMed  Google Scholar 

  • Sidhu GS, Singh AK, Thaloor D, Banaudha KK, Patnaik GK, Srimal RC, Maheshwari RK (1998) Enhancement of wound healing by curcumin in animals. Wound Repair Regen 6:167–177

    Article  CAS  PubMed  Google Scholar 

  • Sidhu GS, Mani H, Gaddipati JP, Singh AK, Seth P, Banaudha KK, Patnaik GK, Maheshwari RK (1999) Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice. Wound Repair Regen 7:362–374

    Article  CAS  PubMed  Google Scholar 

  • Singh S, Khar A (2006) Biological effects of curcumin and its role in cancer chemoprevention and therapy. Anticancer Agents Med Chem 6:259–270

    Article  CAS  PubMed  Google Scholar 

  • Six EM, Ndiaye D, Sauer G, Laabi Y, Athman R, Cumano A, Brou C, Israel A, Logeat F (2004) The notch ligand Delta1 recruits Dlg1 at cell-cell contacts and regulates cell migration. J Biol Chem 279:55818–55826

    Article  CAS  PubMed  Google Scholar 

  • Smalley MJ, Dale TC (1999) Wnt signalling in mammalian development and cancer. Cancer Metastasis Rev 18:215–230

    Article  CAS  PubMed  Google Scholar 

  • Spruck CH, Won KA, Reed SI (1999) Deregulated cyclin E induces chromosome instability. Nature 401:297–300

    Article  CAS  PubMed  Google Scholar 

  • Sreejayan N, Rao MN (1994) Curcuminoids as potent inhibitors of lipid peroxidation. J Pharm Pharmacol 46:1013–1016

    Article  CAS  PubMed  Google Scholar 

  • Sreejayan N, Rao MN (1997) Nitric oxide scavenging by curcuminoids. J Pharm Pharmacol 49:105–107

    Article  CAS  PubMed  Google Scholar 

  • Srinivasan M (1972) Effect of curcumin on blood sugar as seen in a diabetic subject. Indian J Med Sci 26:269–270

    CAS  PubMed  Google Scholar 

  • Srivastava RK (2001) TRAIL/Apo-2 L: mechanisms and clinical applications in cancer. Neoplasia 3:535–546

    Article  CAS  PubMed  Google Scholar 

  • Srivastava RK, Sasaki CY, Hardwick JM, Longo DL (1999a) Bcl-2-mediated drug resistance: inhibition of apoptosis by blocking nuclear factor of activated T lymphocytes (NFAT)-induced Fas ligand transcription. J Exp Med 190:253–265

    Article  CAS  PubMed  Google Scholar 

  • Srivastava RK, Sollott SJ, Khan L, Hansford R, Lakatta EG, Longo DL (1999b) Bcl-2 and Bcl-X(L) block thapsigargin-induced nitric oxide generation, c-Jun NH(2)-terminal kinase activity, and apoptosis. Mol Cell Biol 19:5659–5674

    CAS  PubMed  Google Scholar 

  • Srivastava RK, Chen Q, Siddiqui I, Shankar S (2007) Mechanisms of cell cycle regulation by curcumin in prostate cancer. Front Biosci (In press)

    Google Scholar 

  • Stahl M, Ge C, Shi S, Pestell RG, Stanley P (2006) Notch1-induced transformation of RKE-1 cells requires up-regulation of cyclin D1. Cancer Res 66:7562–7570

    Article  CAS  PubMed  Google Scholar 

  • Stockhausen MT, Kristoffersen K, Poulsen HS (2010) The functional role of Notch signaling in human gliomas. Neuro Oncol 12:199–211

    Article  CAS  PubMed  Google Scholar 

  • Subbaramaiah K, Dannenberg AJ (2003) Cyclooxygenase 2: a molecular target for cancer prevention and treatment. Trends Pharmacol Sci 24:96–102

    Article  CAS  PubMed  Google Scholar 

  • Surh YJ (2002) Anti-tumor promoting potential of selected spice ingredients with antioxidative and anti-inflammatory activities: a short review. Food Chem Toxicol 40:1091–1097

    Article  CAS  PubMed  Google Scholar 

  • Susan M, Rao MN (1992) Induction of glutathione S-transferase activity by curcumin in mice. Arzneimittelforschung 42:962–964

    CAS  PubMed  Google Scholar 

  • Swarnakar S, Ganguly K, Kundu P, Banerjee A, Maity P, Sharma AV (2005) Curcumin regulates expression and activity of matrix metalloproteinases 9 and 2 during prevention and healing of indomethacin-induced gastric ulcer. J Biol Chem 280:9409–9415

    Article  CAS  PubMed  Google Scholar 

  • Takahashi-Yanaga F, Sasaguri T (2008) GSK-3beta regulates cyclin D1 expression: a new target for chemotherapy. Cell Signal 20:581–589

    Article  CAS  PubMed  Google Scholar 

  • Takebe N, Harris PJ, Warren RQ, Ivy SP (2011) Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nat Rev Clin Oncol 8:97–106

    Article  CAS  PubMed  Google Scholar 

  • Tanaka M, Setoguchi T, Hirotsu M, Gao H, Sasaki H, Matsunoshita Y, Komiya S (2009) Inhibition of Notch pathway prevents osteosarcoma growth by cell cycle regulation. Br J Cancer 100:1957–1965

    Article  CAS  PubMed  Google Scholar 

  • Tavera-Mendoza LE, Wang TT, White JH (2006) p19INK4D and cell death. Cell Cycle 5:596–598

    Article  CAS  PubMed  Google Scholar 

  • Taya Y (1997) RB kinases and RB-binding proteins: new points of view. Trends Biochem Sci 22:14–17

    Article  CAS  PubMed  Google Scholar 

  • Tetsu O, McCormick F (1999) Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398:422–426

    Article  CAS  PubMed  Google Scholar 

  • Thaloor D, Miller KJ, Gephart J, Mitchell PO, Pavlath GK (1999) Systemic administration of the NF-kappaB inhibitor curcumin stimulates muscle regeneration after traumatic injury. Am J Physiol 277:C320–C329

    CAS  PubMed  Google Scholar 

  • Thayer SP, di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY, Qi YP, Gysin S, Fernandez-del Castillo C, Yajnik V, Antoniu B, McMahon M, Warshaw AL, Hebrok M (2003) Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 425:851–856

    Article  CAS  PubMed  Google Scholar 

  • Thomasset SC, Berry DP, Garcea G, Marczylo T, Steward WP, Gescher AJ (2007) Dietary polyphenolic phytochemicals–promising cancer chemopreventive agents in humans? A review of their clinical properties. Int J Cancer 120:451–458

    Article  CAS  PubMed  Google Scholar 

  • Traiffort E, Angot E, Ruat M (2010) Sonic Hedgehog signaling in the mammalian brain. J Neurochem 113:576–590

    Article  CAS  PubMed  Google Scholar 

  • Ulasov IV, Nandi S, Dey M, Sonabend AM, Lesniak MS (2011) Inhibition of Sonic hedgehog and Notch pathways enhances sensitivity of CD133(+) glioma stem cells to temozolomide therapy. Mol Med 17:103–112

    Article  CAS  PubMed  Google Scholar 

  • Unnikrishnan MK, Rao MN (1995a) Curcumin inhibits nitrogen dioxide induced oxidation of hemoglobin. Mol Cell Biochem 146:35–37

    Article  CAS  PubMed  Google Scholar 

  • Unnikrishnan MK, Rao MN (1995b) Inhibition of nitrite induced oxidation of hemoglobin by curcuminoids. Pharmazie 50:490–492

    CAS  PubMed  Google Scholar 

  • Valentine SP, Le Nedelec MJ, Menzies AR, Scandlyn MJ, Goodin MG, Rosengren RJ (2006) Curcumin modulates drug metabolizing enzymes in the female Swiss Webster mouse. Life Sci 78:2391–2398

    Article  CAS  PubMed  Google Scholar 

  • Vallejo DM, Caparros E, Dominguez M (2011) Targeting Notch signalling by the conserved miR-8/200 microRNA family in development and cancer cells. EMBO J 30:756–769

    Article  CAS  PubMed  Google Scholar 

  • Verhagen AM, Vaux DL (2002) Cell death regulation by the mammalian IAP antagonist Diablo/Smac. Apoptosis 7:163–166

    Article  CAS  PubMed  Google Scholar 

  • Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE, Moritz RL, Simpson RJ, Vaux DL (2000) Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 102:43–53

    Article  CAS  PubMed  Google Scholar 

  • Verhagen AM, Coulson EJ, Vaux DL (2001) Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs. Genome Biol 2: REVIEWS3009

    Google Scholar 

  • Wahl H, Tan L, Griffith K, Choi M, Liu JR (2007) Curcumin enhances Apo2L/TRAIL-induced apoptosis in chemoresistant ovarian cancer cells. Gynecol Oncol 105:104–112

    Article  CAS  PubMed  Google Scholar 

  • Walker DH, Maller JL (1991) Role for cyclin A in the dependence of mitosis on completion of DNA replication. Nature 354:314–317

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Shelly L, Miele L, Boykins R, Norcross MA, Guan E (2001) Human Notch-1 inhibits NF-kappa B activity in the nucleus through a direct interaction involving a novel domain. J Immunol 167:289–295

    CAS  PubMed  Google Scholar 

  • Wang Z, Zhang Y, Banerjee S, Li Y, Sarkar FH (2006a) Notch-1 down-regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells. Cancer 106:2503–2513

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Zhang Y, Li Y, Banerjee S, Liao J, Sarkar FH (2006b) Down-regulation of Notch-1 contributes to cell growth inhibition and apoptosis in pancreatic cancer cells. Mol Cancer Ther 5:483–493

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Desmoulin S, Banerjee S, Kong D, Li Y, Deraniyagala RL, Abbruzzese J, Sarkar FH (2008) Synergistic effects of multiple natural products in pancreatic cancer cells. Life Sci 83:293–300

    Article  CAS  PubMed  Google Scholar 

  • Wei MC, Lindsten T, Mootha VK, Weiler S, Gross A, Ashiya M, Thompson CB, Korsmeyer SJ (2000) tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev 14:2060–2071

    CAS  PubMed  Google Scholar 

  • Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB, Korsmeyer SJ (2001) Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292:727–730

    Article  CAS  PubMed  Google Scholar 

  • Wei P, Walls M, Qiu M, Ding R, Denlinger RH, Wong A, Tsaparikos K, Jani JP, Hosea N, Sands M, Randolph S, Smeal T (2010) Evaluation of selective gamma-secretase inhibitor PF-03084014 for its antitumor efficacy and gastrointestinal safety to guide optimal clinical trial design. Mol Cancer Ther 9:1618–1628

    Article  CAS  PubMed  Google Scholar 

  • Weinberg RA (1995) The retinoblastoma protein and cell cycle control. Cell 81:323–330

    Article  CAS  PubMed  Google Scholar 

  • Weissenberger J, Priester M, Bernreuther C, Rakel S, Glatzel M, Seifert V, Kogel D (2010) Dietary curcumin attenuates glioma growth in a syngeneic mouse model by inhibition of the JAK1,2/STAT3 signaling pathway. Clin Cancer Res 16:5781–5795

    Article  CAS  PubMed  Google Scholar 

  • Weller M, Krautler N, Mantei N, Suter U, Taylor V (2006) Jagged1 ablation results in cerebellar granule cell migration defects and depletion of Bergmann glia. Dev Neurosci 28:70–80

    Article  CAS  PubMed  Google Scholar 

  • Wend P, Holland JD, Ziebold U, Birchmeier W (2010) Wnt signaling in stem and cancer stem cells. Semin Cell Dev Biol 21:855–863

    Article  CAS  PubMed  Google Scholar 

  • Willis S, Day CL, Hinds MG, Huang DC (2003) The Bcl-2-regulated apoptotic pathway. J Cell Sci 116:4053–4056

    Article  CAS  PubMed  Google Scholar 

  • Wolfel T, Hauer M, Schneider J, Serrano M, Wolfel C, Klehmann-Hieb E, De Plaen E, Hankeln T, Meyer zum Buschenfelde KH, Beach D (1995) A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 269:1281–1284

    Article  CAS  PubMed  Google Scholar 

  • Woodward WA, Chen MS, Behbod F, Alfaro MP, Buchholz TA, Rosen JM (2007) WNT/beta-catenin mediates radiation resistance of mouse mammary progenitor cells. Proc Natl Acad Sci U S A 104:618–623

    Article  CAS  PubMed  Google Scholar 

  • Wu X, Senechal K, Neshat MS, Whang YE, Sawyers CL (1998) The PTEN/MMAC1 tumor suppressor phosphatase functions as a negative regulator of the phosphoinositide 3-kinase/Akt pathway. Proc Natl Acad Sci U S A 95:15587–15591

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto H, Monden T, Miyoshi H, Izawa H, Ikeda K, Tsujie M, Ohnishi T, Sekimoto M, Tomita N, Monden M (1998) Cdk2/cdc2 expression in colon carcinogenesis and effects of cdk2/cdc2 inhibitor in colon cancer cells. Int J Oncol 13:233–239

    CAS  PubMed  Google Scholar 

  • Yamasaki L, Bronson R, Williams BO, Dyson NJ, Harlow E, Jacks T (1998) Loss of E2F-1 reduces tumorigenesis and extends the lifespan of Rb1(+/-)mice. Nat Genet 18:360–364

    Article  CAS  PubMed  Google Scholar 

  • Yan C, Jamaluddin MS, Aggarwal B, Myers J, Boyd DD (2005) Gene expression profiling identifies activating transcription factor 3 as a novel contributor to the proapoptotic effect of curcumin. Mol Cancer Ther 4:233–241

    CAS  PubMed  Google Scholar 

  • Yang K, Proweller A (2011) Vascular smooth muscle Notch signals regulate endothelial cell sensitivity to angiogenic stimulation. J Biol Chem 286:13741–13753

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Hou H, Haller EM, Nicosia SV, Bai W (2005) Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation. EMBO J 24:1021–1032

    Article  CAS  PubMed  Google Scholar 

  • Yang W, Yan HX, Chen L, Liu Q, He YQ, Yu LX, Zhang SH, Huang DD, Tang L, Kong XN, Chen C, Liu SQ, Wu MC, Wang HY (2008) Wnt/beta-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells. Cancer Res 68:4287–4295

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Ikezoe T, Nishioka C, Furihata M, Yokoyama A (2010) AZ960, a novel Jak2 inhibitor, induces growth arrest and apoptosis in adult T-cell leukemia cells. Mol Cancer Ther 9:3386–3395

    Article  CAS  PubMed  Google Scholar 

  • Yao QH, Wang DQ, Cui CC, Yuan ZY, Chen SB, Yao XW, Wang JK, Lian JF (2004) Curcumin ameliorates left ventricular function in rabbits with pressure overload: inhibition of the remodeling of the left ventricular collagen network associated with suppression of myocardial tumor necrosis factor-alpha and matrix metalloproteinase-2 expression. Biol Pharm Bull 27:198–202

    Article  CAS  PubMed  Google Scholar 

  • Yeh TS, Wu CW, Hsu KW, Liao WJ, Yang MC, Li AF, Wang AM, Kuo ML, Chi CW (2009) The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2. Cancer Res 69:5039–5048

    Article  CAS  PubMed  Google Scholar 

  • Yoysungnoen P, Wirachwong P, Bhattarakosol P, Niimi H, Patumraj S (2006) Effects of curcumin on tumor angiogenesis and biomarkers, COX-2 and VEGF, in hepatocellular carcinoma cell-implanted nude mice. Clin Hemorheol Microcirc 34:109–115

    CAS  PubMed  Google Scholar 

  • Yuan XJ, Whang YE (2002) PTEN sensitizes prostate cancer cells to death receptor-mediated and drug-induced apoptosis through a FADD-dependent pathway. Oncogene 21:319–327

    Article  CAS  PubMed  Google Scholar 

  • Zbinden M, Duquet A, Lorente-Trigos A, Ngwabyt SN, Borges I, Ruiz i Altaba A (2010) NANOG regulates glioma stem cells and is essential in vivo acting in a cross-functional network with GLI1 and p53. EMBO J 29:2659–2674

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Wang H, Ikeda S, Fahey F, Bielenberg D, Smits P, Hauschka PV (2010) Notch3 in human breast cancer cell lines regulates osteoblast-cancer cell interactions and osteolytic bone metastasis. Am J Pathol 177:1459–1469

    Article  CAS  PubMed  Google Scholar 

  • Zou H, Henzel WJ, Liu X, Lutschg A, Wang X (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90:405–413

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the grants from the National Institutes of Health, Kansas Bioscience Authority, and the Department of Defense, US Army. We thank all the lab members for critically reading the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sharmila Shankar .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Shankar, S., Srivastava, R.K. (2012). Curcumin: Structure, Biology and Clinical Applications. In: Shankar, S., Srivastava, R. (eds) Nutrition, Diet and Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2923-0_17

Download citation

Publish with us

Policies and ethics