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Phytoconstituents as apoptosis inducing agents: strategy to combat cancer

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Abstract

Advancement in the field of cancer molecular biology has aided researchers to develop various new chemopreventive agents which can target cancer cells exclusively. Cancer chemopreventive agents have proficiency to inhibit, reverse and delay process of carcinogenesis during its early and later course. Chemopreventive agents can act as antioxidative, antimutagenic/antigenotoxic, anti-inflammatory agents or via aiming various molecular targets in a cell to induce cell death. Apoptosis is a kind of cell death which shows various cellular morphological alterations such as cell shrinkage, blebbing of membrane, chromatin condensation, DNA fragmentation, formation of apoptotic bodies etc. Nowadays, apoptosis is being one of the new approaches for the identification and development of novel anticancer therapies. For centuries, plants are known to play part in daily routine from providing food to management of human health. In the last two decades, diverse phytochemicals and various botanical formulations have been characterized as agents that possess potential to execute cancer cells via inducing apoptosis. Data obtained from the research carried out globally pointed out that natural products are the potential candidates which have capability to combat cancer. In the present review, we surveyed literature on natural products which throws light on the mechanism through which these phytochemicals induce apoptosis in cancer cells.

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References

  • Aggarwal BB (2004) Nuclear factor-kappaB: the enemy within. Cancer Cell 6:203–208

    Article  CAS  Google Scholar 

  • Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J (1996) Human ICE/CED-3 protease nomenclature. Cell 87:171

    Article  CAS  Google Scholar 

  • American Cancer Society (2014) Cancer facts & figures 2014. American Cancer Society, Atlanta

    Google Scholar 

  • Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants and degenerative diseases of aging. Proc Natl Acad Sci USA 90:7915–7922

    Article  CAS  Google Scholar 

  • Amin AR, Kucuk O, Khuri FR, Shin DM (2009) Perspectives for cancer prevention with natural compounds. J Clin Oncol 27:2712–2725

    Article  CAS  Google Scholar 

  • Angel P, Karin M (1991) The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta 1072:129–157

    CAS  Google Scholar 

  • Angel P, Imagawa M, Chiu R, Stein B, Imbra RJ, Rahmsdorf HJ, Jonat C, Herrlich P, Karin M (1987) Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell 49:729–739

    Article  CAS  Google Scholar 

  • Arends MJ, Wyllie AH (1991) Apoptosis: mechanisms and roles in pathology. Int Rev Exp Pathol 32:223–254

    Article  CAS  Google Scholar 

  • Auyeung KK-W, Mok N-L, Wong C-M, Cho C-H, Ko JK-S (2010) Astragalus saponins modulate mTOR and ERK signaling to promote apoptosis through the extrinsic pathway in HT-29 colon cancer cells. Int J Mol Med 26:341–349

    CAS  Google Scholar 

  • Bae YS, Kang SW, Seo MS, Baines IC, Tekle E, Chock PB, Rhee SG (1997) Epidermal growth factor (EGF)-induced generation of hydrogen peroxide. J Biol Chem 272:217–221

    Article  CAS  Google Scholar 

  • Baldwin AS (1996) The NF-kB and IkB proteins: new discoveries and insights. Annu Rev Immunol 14:649–681

    Article  CAS  Google Scholar 

  • Balunas MJ, Kinghorn AD (2005) Drug discovery from medicinal plants. Life Sci 78:431–441

    Article  CAS  Google Scholar 

  • Bar PR (1996) Apoptosis-the cell’s silent exit. Life Sci 59:369–378

    Article  CAS  Google Scholar 

  • Behrend L, Henderson G, Zwacka RM (2003) Reactive oxygen species in oncogenic transformation. Biochem Soc Trans 31:1441–1444

    Article  CAS  Google Scholar 

  • Benarba B, Meddah B, Aoues A (2012) Bryonia dioica aqueous extract induces apoptosis through mitochondrial intrinsic pathway in BL41 Burkitt’s lymphoma cells. J Ethnopharmacol 141:510–516

    Article  CAS  Google Scholar 

  • Benz CC, Yau C (2008) Ageing, oxidative stress and cancer: paradigms in parallax. Nat Rev Cancer 8:875–879

    Article  CAS  Google Scholar 

  • Bohmann D, Bos TJ, Admon A, Nishimura T, Vogt PK, Tjian R (1987) Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science 238:1386–1392

    Article  CAS  Google Scholar 

  • Bossy-Wetzel E, Green DR (1999) Apoptosis: checkpoint at the mitochondrial frontier. Mutat Res 434:243–251

    Article  CAS  Google Scholar 

  • Brohem CA, Sawada TC, Massaro RR, Almeida RL, Rivelli DP, Ropke CD, da Silva VV, de Lima TM, Curi R, Barros SB, Maria-Engler SS (2009) Apoptosis induction by 4-nerolidylcatechol in melanoma cell lines. Toxicol In Vitro 23:111–119

    Article  CAS  Google Scholar 

  • Brunner T, Wasem C, Torgler R, Cima I, Jakob S, Corazza N (2003) Fas (CD95/Apo-1) ligand regulation in T cell homeostasis, cell-mediated cytotoxicity and immune pathology. Semin Immunol 15:167–176

    Article  CAS  Google Scholar 

  • Calixto JB (2005) Twenty-five years of research on medicinal plants in Latin America A personal view. J Ethnopharmacol 100:131–134

    Article  Google Scholar 

  • Cano E, Mahadevan LC (1995) Parallel signal processing among mammalian MAPKs. Trends Biochem Sci 20:117–122

    Article  CAS  Google Scholar 

  • Chen FE, Ghosh G (1999) Regulation of DNA binding by Rel/NF-kappaB transcription factors: structural views. Oncogene 18:6845–6852

    Article  CAS  Google Scholar 

  • Chen LF, Greene WC (2004) Shaping the nuclear action of NF-kB. Nature Rev Mol Cell Biol 5:392–401

    Article  CAS  Google Scholar 

  • Chen YR, Wang X, Templeton D, Davis RJ, Tan TH (1996) The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and gamma radiation. Duration of JNK activation may determine cell death and proliferation. J Biol Chem 271:31929–31936

    Article  CAS  Google Scholar 

  • Chen CY, Liu TZ, Tseng WC, Lu FJ, Hung RP, Chen CH, Chen CH (2008) (−)-Anonaine induces apoptosis through Bax- and caspase-dependent pathways in human cervical cancer (HeLa) cells. Food Chem Toxicol 46:2694–2702

    Article  CAS  Google Scholar 

  • Chen HM, Wu YC, Chia YC, Chang FR, Hsu HK, Hsieh YC, Chen CC, Yuan SS (2009) Gallic acid, a major component of Toona sinensis leaf extracts, contains a ROS-mediated anti-cancer activity in human prostate cancer cells. Cancer Lett 286:161–171

    Article  CAS  Google Scholar 

  • Chidambara Murthy KN, Jayaprakasha GK, Patil BS (2011) Obacunone and obacunone glucoside inhibit human colon cancer (SW480) cells by the induction of apoptosis. Food Chem Toxicol 49:1616–1625

    Article  CAS  Google Scholar 

  • Chowdhury I, Tharakan B, Bhat GK (2008) Caspases—an update. Comp Biochem Physiol B Part B 151:10–27

    Article  CAS  Google Scholar 

  • Circu ML, Aw TY (2010) Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med 48:749–762

    Article  CAS  Google Scholar 

  • Colgate EC, Miranda CL, Stevens JF, Bray TM, Ho E (2007) Xanthohumol, a prenylflavonoid derived from hops induces apoptosis and inhibits NF-kappaB activation in prostate epithelial cells. Cancer Lett 8:201–209

    Article  CAS  Google Scholar 

  • Conklin KA (2004) Cancer chemotherapy and antioxidants. J. Nutrition 134:3201–3204

    Google Scholar 

  • Controlling Cancer in Developing Countries: Prevention and Treatment Strategies Merit Further Study. Disease Control Priorities Project. April 2007

  • Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2:647–656

    Article  CAS  Google Scholar 

  • D’Autreaux B, Toledano MB (2007) ROS as signaling molecules: mechanisms that generate specificity in ROS homeostasis. Nature Rev Mol Cell Biol 8:813–824

    Article  CAS  Google Scholar 

  • Dahanukar SA, Kulkarni RA, Rege NN (2000) Pharmacology of medicinal plants and natural products. Indian J Pharmacol 32:S81–S118

    CAS  Google Scholar 

  • Debnath J, Baehrecke EH, Kroemer G (2005) Does autophagy contribute to cell death? Autophagy 1:66–74

    Article  CAS  Google Scholar 

  • Deveraux QL, Roy N, Stennicke HR, Van Arsdale T, Zhou Q, Srinivasula SM, Alnemri ES, Salvesen GS, Reed JC (1998) IAPs block apoptotic events induced by caspase-8 and cytochrome C by direct inhibition of distinct caspases. EMBO J 17:2215–2223

    Article  CAS  Google Scholar 

  • Dhillon H, Chikara S, Reindl KM (2014) Piperlongumine induces pancreatic cancer cell death by enhancing reactive oxygen species and DNA damage. Toxicol Rep. 1:309–318

    Article  CAS  Google Scholar 

  • Dickinson SE, Melton TF, Olson ER, Zhang J, Saboda K, Bowden GT (2009) Inhibition of activator protein-1 by sulforaphane involves interaction with cysteine in the cFos DNA-binding domain: implications for chemoprevention of UVB-induced skin cancer. Cancer Res 69:7103–7110

    Article  CAS  Google Scholar 

  • Ding M, Lu Y, Bowman L, Huang C, Leonard S, Wang L, Vallyathan V, Castranova V, Shi X (2004) Inhibition of AP-1 and neoplastic transformation by fresh apple peel extract. J Biol Chem 279:10670–10676

    Article  CAS  Google Scholar 

  • Ding M, Zhao J, Bowman L, Lu Y, Shi X (2010) Inhibition of AP-1 and MAPK signaling and activation of Nrf2/ARE pathway by quercitrin. Int J Oncol 36:59–67

    CAS  Google Scholar 

  • Dolcet X, Llobet D, Pallares J, Matias-Guiu X (2005) NF-kB in development and progression of human cancer. Virchows Arch 446:475–482

    Article  CAS  Google Scholar 

  • Doll R, Peto R (1981) The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst 66:1191–1308

    CAS  Google Scholar 

  • Donzelli M, Draetta GF (2003) Regulating mammalian checkpoints through Cdc25 inactivation. EMBO Rep 4:671–677

    Article  CAS  Google Scholar 

  • Dorai T, Aggarwal B (2004) Role of chemopreventive agents in cancer therapy. Cancer Lett 215:129–140

    Article  CAS  Google Scholar 

  • Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:4495–4516

    Article  CAS  Google Scholar 

  • Fan Z, Beresford PJ, Zhang D, Lieberman J (2002) HMG2 interacts with the nucleosome assembly protein SET and is a target of the cytotoxic T-lymphocyte protease granzyme A. Mol Cell Biol 22:2810–2820

    Article  CAS  Google Scholar 

  • Fan Z, Beresford PJ, Oh DY, Zhang D, Lieberman J (2003a) Tumor Suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein set is its inhibitor. Cell 112:659–672

    Article  CAS  Google Scholar 

  • Fan Z, Beresford PJ, Zhang D, Xu Z, Novina CD, Yoshida A, Pommier Y, Lieberman J (2003b) Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A. Nature Immunol 4:145–153

    Article  CAS  Google Scholar 

  • Feng R, Bowman LL, Lu Y, Leonard SS, Shi X, Jiang H-H, Castranova V, Vallyathan V, Ding M (2004) Blackberry extracts inhibit activating protein 1 activation and cell transformation by perturbing the mitogenic signaling pathway. Nutr Cancer 50:80–89

    Article  Google Scholar 

  • Ferreira PM, Santos AG, Tininis AG, Costa PM, Cavalheiro AJ, Bolzani VS, Moraes MO, Costa-Lotufo LV, Montenegro RC, Pessoa C (2010) Casearin X exhibits cytotoxic effects in leukemia cells triggered by apoptosis. Chem Biol Interact 188:497–504

    Article  CAS  Google Scholar 

  • Fritz R, Bol J, Hebling U, Angermuller S, Volkl A, Fahimi HD, Mueller S (2007) Compartment-dependent management of H2O2 by peroxisomes. Free Radic Biol Med 42:1119–1129

    Article  CAS  Google Scholar 

  • Fruehauf JP, Meyskens FL Jr (2007) Reactive oxygen species: a breath of life or death? Clin Cancer Res 13:789–794

    Article  CAS  Google Scholar 

  • Gambari R, Borgatti M, Lampronti I, Fabbri E, Brognara E, Bianchi N, Piccagli L, Yuen MC, Kan CW, Hau DK, Fong WF, Wong WY, Wong RS, Chui CH (2012) Corilagin is a potent inhibitor of NF-kappaB activity and downregulates TNF-alpha induced expression of IL-8 gene in cystic fibrosis IB3-1 cells. Int Immunopharmacol 13:308–315

    Article  CAS  Google Scholar 

  • Garg A, Aggarwal BB (2002) Nuclear transcription factor-kappaB as a target for cancer drug development. Leukemia 16:1053–1068

    Article  CAS  Google Scholar 

  • Ghosh S, Karin M (2002) Missing pieces in the NF-kB puzzle. Cell 109:S81–S96

    Article  CAS  Google Scholar 

  • Gilmore TD, Herscovitch M (2006) Inhibitors of NF-kappaB signaling: 785 and counting. Oncogene 25:6887–6899

    Article  CAS  Google Scholar 

  • Gong K, Li W (2011) Shikonin, a Chinese plant-derived naphthoquinone, induces apoptosis in hepatocellular carcinoma cells through reactive oxygen species: a potential new treatment for hepatocellular carcinoma. Free Radic Biol Med 51:2259–2271

    Article  CAS  Google Scholar 

  • Gordaliza M (2007) Natural products as lead to anticancer drugs. Clin Transl Oncol 9:767–776

    Article  CAS  Google Scholar 

  • Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281:1309–1312

    Article  CAS  Google Scholar 

  • Grimm S, Baeurle PA (1993) The inducible transcription factor NF-kappaB: structure-function relationship of its protein subunits. Biochem J 290:297–308

    Article  CAS  Google Scholar 

  • Grütter MG (2000) Caspases: key players in programmed cell death. Curr Opin Struct Biol 10:649–655

    Article  Google Scholar 

  • Guyton KZ, Liu Y, Gorospe M, Xu Q, Holbrook NJ (1996) Activation of mitogen-activated protein kinase by H2O2: role in cell survival following oxidant injury. J Biol Chem 271:4138–4142

    Article  CAS  Google Scholar 

  • Hajiaghaalipour F, Kanthimathi MS, Sanusi J, Rajarajeswaran J (2015) White tea (Camellia sinensis) inhibits proliferation of the colon cancer cell line, HT-29, activates caspases and protects DNA of normal cells against oxidative damage. Food Chem 169:401–410

    Article  CAS  Google Scholar 

  • Halliwell B, Cross CE (1994) Oxygen-derived species: their relation to human disease and environmental stress. Environ Health Perspect 102:5–12

    Article  CAS  Google Scholar 

  • Hamsa TP, Kuttan G (2011) Harmine activates intrinsic and extrinsic pathways of apoptosis in B16F-10 melanoma. Chin Med 6:11. doi:10.1186/1749-8546-6-11

    Article  CAS  Google Scholar 

  • Han SS, Keum YS, Seo HJ, Surh YJ (2002) Curcumin suppresses activation of NF-κB and AP-1 induced by phorbol ester in cultured human promyelocytic leukemia cells. J Biochem Mol Biol 35:337–342

    Article  CAS  Google Scholar 

  • Havelek R, Seifrtova M, Kralovec K, Bruckova L, Cahlikova L, Dalecka M, Vavrova J, Rezacova M, Opletal L, Bilkova Z (2014) The effect of Amaryllidaceae alkaloids haemanthamine and haemanthidine on cell cycle progression and apoptosis in p53-negative human leukemic Jurkat cells. Phytomedicine 21:479–490

    Article  CAS  Google Scholar 

  • Hayden MS, Ghosh S (2004) Signaling to NF-kappaB. Genes Dev 18:2195–2224

    Article  CAS  Google Scholar 

  • Hostanska K, Reichling J, Bommer S, Weber M, Saller R (2003) Hyperforin a constituent of St John’s wort (Hypericum perforatum L.) extract induces apoptosis by triggering activation of caspases and with hypericin synergistically exerts cytotoxicity towards human malignant cell lines. Eur J Pharm Biopharm 56:121–132

    Article  CAS  Google Scholar 

  • Hsieh TJ, Liu TZ, Lu FJ, Hsieh PY, Chen CH (2006) Actinodaphnine induces apoptosis through increased nitric oxide, reactive oxygen species and down regulation of NF-kappa B signaling in human hepatoma Mahlavu cells. Food Chem Toxicol 44:344–354

    Article  CAS  Google Scholar 

  • Hsu H-F, Huang K-H, Lu K-J, Chiou S-J, Yen J-H, Chang C-C, Houng J-Y (2011) Typhonium blumei extract inhibits proliferation of human lung adenocarcinoma A549 cells via induction of cell cycle arrest and apoptosis. J Ethnopharmacol 135:492–500

    Article  Google Scholar 

  • Hsum YW, Yew WT, Hong PL, Soo KK, Hoon LS, Chieng YC, Mooi LY (2011) Cancer chemopreventive activity of maslinic acid: suppression of COX-2 expression and inhibition of NF-κB and AP-1 activation in Raji cells. Planta Med 77:152–157

    Article  CAS  Google Scholar 

  • Hu W, Kavanagh JJ (2003) Anticancer therapy targeting the apoptotic pathway. Lancet Oncol 4:721–729

    Article  CAS  Google Scholar 

  • Hu X, Zhang X, Qiu S, Yu D, Lin S (2010) Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells. Biochem Biophys Res Commun 398:62–67

    Article  CAS  Google Scholar 

  • Huang C, Ma W-Y, Young MR, Colburn N, Dong Z (1998) Shortage of mitogen-activated protein kinase is responsible for resistance to AP-1 transactivation and transformation in mouse JB6 cells. Proc Natl Acad Sci USA 95:156–161

    Article  CAS  Google Scholar 

  • Inayat-Hussain SH, Osman AB, Din LB, Ali AM, Snowden RT, MacFarlane M, Cain K (1999) Caspases-3 and -7 are activated in goniothalamin-induced apoptosis in human Jurkat T-cells. FEBS Lett 456:379–383

    Article  CAS  Google Scholar 

  • Ishiguro K, Ando T, Maeda O, Ohmiya N, Niwa Y, Kadomatsu K, Goto H (2007) Ginger ingredients reduce viability of gastric cancer cells via distinct mechanisms. Biochem Biophys Res Commun 362:218–223

    Article  CAS  Google Scholar 

  • Ito C, Itoigawa M, Nakao K, Murata T, Tsuboi M, Kaneda N, Furukawa H (2006) Induction of apoptosis by carbazole alkaloids isolated from Murraya koenigii. Phytomedicine 13:359–365

    Article  CAS  Google Scholar 

  • Jeong S-Y, Seol D-W (2008) The role of mitochondria in apoptosis. BMB reports 41:11–22

    Article  CAS  Google Scholar 

  • Ji S, Orlikova B, Diederich M (2014) Non-edible plants as an attractive source of compounds with chemopreventive potential. J Cancer Prev 19:1–6

    Article  Google Scholar 

  • Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nature Rev Genet 3:415–428

    Article  CAS  Google Scholar 

  • Juin P, Geneste O, Raimbaud E, Hickman JA (2004) Shooting at survivors: BCL-2 family members as drug targets for cancer. Biochim Biophys Acta 1644:251–260

    Article  CAS  Google Scholar 

  • Ka H, Park HJ, Jung HJ, Choi JW, Cho KS, Ha J, Lee KT (2003) Cinnamaldehyde induces apoptosis by ROS-mediated mitochondrial permeability transition in human promyelocytic leukemia HL-60 cells. Cancer Lett 196:143–152

    Article  CAS  Google Scholar 

  • Kam PCA, Ferch NI (2000) Apoptosis: mechanisms and clinical implications. Anaesthesia 55:1081–1093

    Article  CAS  Google Scholar 

  • Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    Article  CAS  Google Scholar 

  • Khan M, Giessrigl B, Vonach C, Madlener S, Prinz S, Herbaceck I, Hölzl C, Bauer S, Viola K, Mikulits W, Quereshi RA, Knasmüller S, Grusch M, Kopp B, Krupitza G (2010) Berberine and a Berberis lycium extract inactivate Cdc25A and induce α-tubulin acetylation that correlate with HL-60 cell cycle inhibition and apoptosis. Mutat Res 683:123–130

    Article  CAS  Google Scholar 

  • Kiechle FL, Zhang X (2002) Apoptosis: biochemical aspects and clinical implications. Clin Chim Acta 326:27–45

    Article  CAS  Google Scholar 

  • Kim EJ, Lee YJ, Shin HK, Park JH (2005) Induction of apoptosis by the aqueous extract of Rubus coreanum in HT-29 human colon cancer cells. Nutrition 21:1141–1148

    Article  Google Scholar 

  • Kim JY, Yoon MY, Cha MR, Hwang JH, Park E, Choi SU, Park HR, Hwang YI (2007) Methanolic extracts of Plocamium telfairiae induce cytotoxicity and caspase-dependent apoptosis in HT-29 human colon carcinoma cells. J Med Food 10:587–593

    Article  CAS  Google Scholar 

  • Kim KC, Kim JS, Son JK, Kim IG (2007) Enhanced induction of mitochondrial damage and apoptosis in human leukemia HL-60 cells by the Ganoderma lucidum and Duchesnea chrysantha extracts. Cancer Lett 246:210–217

    Article  CAS  Google Scholar 

  • Kim EJ, Lim SS, Park SY, Shin HK, Kim JS, Park JHY (2008) Apoptosis of DU145 human prostate cancer cells induced by dehydrocostus lactone isolated from the root of Saussurea lappa. Food Chem Toxicol 46:3651–3658

    Article  CAS  Google Scholar 

  • Kim H, Kim H, Mosaddik A, Gyawali R, Ahn KS, Cho SK (2012) Induction of apoptosis by ethanolic extract of mango peel and comparative analysis of the chemical constitutes of mango peel and flesh. Food Chem 133:416–422

    Article  CAS  Google Scholar 

  • Kirshner JR, He S, Balasubramanyam V, Kepros J, Yang CY, Zhang M, Du Z, Barsoum J, Bertin J (2008) Elesclomol induces cancer cell apoptosis through oxidative stress. Mol Cancer Ther 7:2319–2327

    Article  CAS  Google Scholar 

  • Kischkel FC, Hellbartdt S, Behrmann I, Germer M, Pawlita M, Krammer PH, Peter ME (1995) Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signalling complex (DISC) with the receptor. EMBO J 14:5579–5588

    CAS  Google Scholar 

  • Klaunig JE, Kamendulis LM (2004) The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol 44:239–267

    Article  CAS  Google Scholar 

  • Kong Q, Beel JA, Lillehei KO (2000) A threshold concept for cancer therapy. Med Hypotheses 55:29–35

    Article  CAS  Google Scholar 

  • Kumar S, Vaux DL (2002) Apoptosis. A cinderella caspase takes center stage. Science 297:1290–1291

    Article  CAS  Google Scholar 

  • Kummalue T, Sujiwattanarat P, Jiratchariyakul W (2011) Apoptotic inducibility of Sapindus rarax water extract on A549 human lung cancer cell line. J Med Plants Res 5:1087–1094

    Google Scholar 

  • Kuo YF, Su YZ, Tseng YH, Wang SY, Wang HM, Chueh PJ (2010) Flavokawain B, a novel chalcone from Alpinia pricei Hayata with potent apoptotic activity: Involvement of ROS and GADD153 upstream of mitochondria-dependent apoptosis in HCT116 cells. Free Radic Biol Med 49:214–226

    Article  CAS  Google Scholar 

  • Kuwana T, Mackey MR, Perkins G, Ellisman MH, Latterich M, Schneiter R, Green DR, Newmeyer DD (2002) Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 111:331–342

    Article  CAS  Google Scholar 

  • Kwon HJ, Hong YK, Kim KH, Han CH, Cho SH, Choi JS, Kim B-W (2006) Methanolic extract of Pterocarpus santalinus induces apoptosis in HeLa cells. J Ethnopharmacol 105:229–234

    Article  CAS  Google Scholar 

  • Kwon HK, Hwang JS, So JS, Lee CG, Sahoo A, Ryu JH, Jeon WK, Ko BS, Im CR, Lee SH, Park ZY, Im SH (2010) Cinnamon extract induces tumor cell death through inhibition of NFκB and AP1. BMC Cancer 10:392–402

    Article  Google Scholar 

  • Kyriakis JM, Avruch J (1996) Protein kinase cascades activated by stress and inflammatory cytokines. BioEssays 18:567–577

    Article  CAS  Google Scholar 

  • Lee JC, Won SJ, Chao CL, Wu FL, Liu HS, Ling P (2008) Morusin induces apoptosis and suppresses NF-kB activity in human colorectal cancer HT-29 cells. Biochem Biophys Res Commun 372:236–242

    Article  CAS  Google Scholar 

  • Lei JC, Yu JQ, Yin Y, Liu YW (2012) Zou GL (2012) Alantolactone induces activation of apoptosis in human hepatoma cells. Food Chem Toxicol 50:3313–3319

    Article  CAS  Google Scholar 

  • Li YC, Tyan YS, Kuo HM, Chang WC, Hsia TC, Chung JG (2004) Baicalein induced in vitro apoptosis undergo caspases activity in human promyelocytic leukemia HL-60 cells. Food Chem Toxicol 42:37–43

    Article  CAS  Google Scholar 

  • Li H, Wang LJ, Qiu GF, Yu JQ, Liang SC, Hu XM (2007) Apoptosis of Hela cells induced by extract from Cremanthodium humile. Food Chem Toxicol 45:2040–2046

    Article  CAS  Google Scholar 

  • Li S, Dong P, Wang J, Zhang J, Gu J, Wu X, Wu W, Fei X, Zhang Z, Wang Y, Quan Z, Liu Y (2010) Icariin, a natural flavonol glycoside, induces apoptosis in human hepatoma SMMC-7721 cells via a ROS/JNK-dependent mitochondrial pathway. Cancer Lett 298:222–230

    Article  CAS  Google Scholar 

  • Li X, Huang Q, Ong Choon-Nam, Yang Xing-Fen, Shen Han-Ming (2010) Chrysin sensitizes tumor necrosis factor-α-induced apoptosis in human tumor cells via suppression of nuclear factor-kappaB. Cancer Lett 293:109–116

    Article  CAS  Google Scholar 

  • Lieberman J, Fan Z (2003) Nuclear war: the granzyme A-bomb. Curr Opin Immunol 15:553–559

    Article  CAS  Google Scholar 

  • Lim HK, Moon JY, Kim H, Cho M, Cho SK (2009) Induction of apoptosis in U937 human leukaemia cells by the hexane fraction of an extract of immature Citrus grandis Osbeck fruits. Food Chem 114:1245–1250

    Article  CAS  Google Scholar 

  • Lin A, Karin M (2003) NF-kB in cancer: a marked target. Semin Cancer Biol 13:107–114

    Article  CAS  Google Scholar 

  • Lin C-H, Lu W-C, Wang C-W, Chan Y-C, Chen M-K (2013) Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells. BMC Complement Altern Med. 13:46. doi:10.1186/1472-6882-13-46

    Article  CAS  Google Scholar 

  • Lippens S, Kockx M, Knaapen M, Mortier L, Polakowska R, Verheyen A, Garmyn M, Zwijsen A, Formstecher P, Huylebroeck D, Vandenabeel P, Declercq W (2000) Epidermal differentiation does not involve the pro-apoptotic executioner caspases, but is associated with caspase-14 induction and processing. Cell Death Differ 7:1218–1224

    Article  CAS  Google Scholar 

  • Liu J, Li Y, Ren W, Hu W-X (2006) Apoptosis of HL-60 cells induced by extracts from Narcissus tazetta var. chinensis. Cancer Lett 242:133–140

    Article  CAS  Google Scholar 

  • Liu B, Cheng Y, Zhang B, Bian HJ, Bao JK (2009) Polygonatum cyrtonema lectin induces apoptosis and autophagy in human melanoma A375 cells through a mitochondria-mediated ROS-p38-p53 pathway. Cancer Lett 275:54–60

    Article  CAS  Google Scholar 

  • Lü CX, Fan TJ, Hu GB, Cong RS (2003) Apoptosis-inducing factor and apoptosis. Acta Biochim Biophys Sin 35:881–885

    Google Scholar 

  • Lundqvist J, Yde CW, Lykkesfeldt AE (2014) 1α, 25-dihydroxyvitamin D3 inhibits cell growth and NFκB signaling in tamoxifen-resistant breast cancer cells. Steroids 85:30–35

    Article  CAS  Google Scholar 

  • MacLachlan TK, Sang N, Giordano A (1995) Cyclins, cyclin-dependent kinases and Cdk inhibitors: implications in cell cycle control and cancer. Crit Rev Eukaryot Gene Expr 5:127–156

    Article  CAS  Google Scholar 

  • Mahata S, Bharti AC, Shukla S, Tyagi A, Husain SA, Das BC (2011) Berberine modulates AP-1 activity to suppress HPV transcription and downstream signaling to induce growth arrest and apoptosis in cervical cancer cells. Mol Cancer 10:39–53

    Article  CAS  Google Scholar 

  • Manna SK, Zhang HJ, Yan T, Oberley LW, Aggarwal BB (1998) Overexpression of manganese superoxide dismutase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription fac-tor-b and activated protein-1. J Biol Chem 273:13245–13254

    Article  CAS  Google Scholar 

  • Manohar M, Fatima I, Saxena R, Chandra V, Sankhwar PL, Dwived A (2013) (−)-Epigallocatechin-3-gallate induces apoptosis in human endometrial adenocarcinoma cells via ROS generation and p38 MAP kinase activation. J Nutr Biochem 24:940–947

    Article  CAS  Google Scholar 

  • Manson MM (2003) Cancer prevention: the potential for diet to modulate molecular signalling. Trends Mol Med 9:11–18

    Article  CAS  Google Scholar 

  • Manu K, Kuttan G (2008) Ursolic acid induces apoptosis by activating p53 and caspase-3 gene expressions and suppressing NF-κB mediated activation of bcl-2 in B16F-10 melanoma cells. Int Immunopharmacol 8:974–981

    Article  CAS  Google Scholar 

  • Martinou JC, Desagher S, Antonsson B (2000) Cytochrome c release from mitochondria: all or nothing. Nature Cell Biol 2:E41–E43

    Article  CAS  Google Scholar 

  • McCarthy NJ, Evan GI (1998) Methods for detecting and quantifying apoptosis. Curr Top Dev Biol 36:259–278

    Article  CAS  Google Scholar 

  • McConkey DJ, Zhivotovsky B, Orrenius S (1996) Apoptosis molecular mechanisms and biomedical implications. Mol Aspects Med 17:1–10

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  • McLachlan A, Kekre N, McNulty J, Pandey S (2005) Pancratistatin: a natural anti-cancer compound that targets mitochondria specifically in cancer cells to induce apoptosis. Apoptosis 10:619–630

    Article  CAS  Google Scholar 

  • Mishra KP, Padwad YS, Dutta A, Ganju L, Sairam M, Banerjee PK, Sawhney RC (2008) Aqueous extract of Rhodiola imbricata rhizome inhibits proliferation of an erythroleukemic cell line K-562 by inducing apoptosis and cell cycle arrest at G2/M phase. Immunobiology 213:125–131

    Article  CAS  Google Scholar 

  • Mohan S, Abdelwahab SI, Kamalidehghan B, Syam S, May KS, Harmal NS, Shafifiyaz N, Hadi AH, Hashim NM, Rahmani M, Taha MM, Cheah SC, Zajmi A (2012) Involvement of NF-κB and Bcl2/Bax signaling pathways in the apoptosis of MCF7 cells induced by a xanthone compound Pyranocycloartobiloxanthone A. Phytomedicine 19:1007–1015

    Article  CAS  Google Scholar 

  • Moon DO, Kim MO, Choi YH, Hyun JW, Chang WY, Kim GY (2010) Butein induces G(2)/M phase arrest and apoptosis in human hepatoma cancer cells through ROS generation. Cancer Lett 288:204–213

    Article  CAS  Google Scholar 

  • Moon JY, Mosaddik A, Kim H, Cho M, Choi HK, Kim YS, Cho SK (2011) The chloroform fraction of guava (Psidium cattleianum sabine) leaf extract inhibits human gastric cancer cell proliferation via induction of apoptosis. Food Chem 125:369–375

    Article  CAS  Google Scholar 

  • Mousavi SH, Tavakkol-Afshari J, Brook A, Jafari-Anarkooli I (2009) Role of caspases and Bax protein in saffron-induced apoptosis in MCF-7 cells. Food Chem Toxicol 47:1909–1913

    Article  CAS  Google Scholar 

  • Naidu VG, Mahesh BU, Giddam AK, Babu KR, Ding J, Ramesh B, Ramesh B, Gopalakrishnakone P (2013) Apoptogenic activity of ethyl acetate extract of leaves of Memecylon edule on human gastric carcinoma cells via mitochondrial dependent pathway. Asian Pac J Trop Med 6:337–345

    Article  CAS  Google Scholar 

  • Newman DJ, Cragg GM, Snader KM (2003) Natural products as sources of new drugs over the period 1981–2002. J Nat Prod 66:1022–1037

    Article  CAS  Google Scholar 

  • Nicholson DW (1999) Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ 6:1028–1042

    Article  CAS  Google Scholar 

  • Nicholson DW (2000) From bench to clinic with apoptosis-based therapeutic agents. Nature 407:810–816

    Article  CAS  Google Scholar 

  • Oh JH, Bana JO, Choa MC, Joa M, Junga JK, Ahnc B, Yoond DY, Hana SB, Honga JT (2012) 4-O-methylhonokiol inhibits colon tumor growth via p21-mediated suppression of NF-κB activity. J Nutr Biochem 23:706–715

    Article  CAS  Google Scholar 

  • Oltvai Z, Milliman C, Korsmeyer S (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609–619

    Article  CAS  Google Scholar 

  • Ovadje P, Chatterjee S, Griffin C, Tran C, Hamm C, Pandey S (2011) Selective induction of apoptosis through activation of caspase-8 in human leukemia cells (Jurkat) by dandelion root extract. J Ethnopharmacol 133:86–91

    Article  CAS  Google Scholar 

  • Pal HC, Sehar I, Bhushan S, Gupta BD, Saxena AK (2010) Activation of caspases and poly (ADP-ribose) polymerase cleavage to induce apoptosis in leukemia HL-60 cells by Inula racemosa. Toxicol In Vitro 24:1599–1609

    Article  CAS  Google Scholar 

  • Pan MH, Ghai G, Ho CT (2008) Food bioactives, apoptosis, and cancer. Mol Nutr Food Res 52:43–52

    Article  CAS  Google Scholar 

  • Panchal RG (1998) Novel therapeutic strategies to selectively kill cancer cells. Biochem Pharmacol 55:247–252

    Article  CAS  Google Scholar 

  • Pardhasaradhi BV, Reddy M, Ali AM, Kumari AL, Khar A (2004) Antitumour activity of Annona squamosa seed extracts is through the generation of free radicals and induction of apoptosis. Indian J Biochem Biophys 41:167–172

    CAS  Google Scholar 

  • Park HJ, Kim YJ, Leem K, Park SJ, Seo JC, Kim HK, Chung JH (2005) Coptis japonica root extract induces apoptosis through caspase 3 activation in SNU-668 human gastric cancer cells. Phytother Res 19:189–192

    Article  CAS  Google Scholar 

  • Park KR, Nam D, Yun HM, Lee SG, Jang HJ, Sethi G, Cho SK, Ahn KS (2011) β-Caryophyllene oxide inhibits growth and induces apoptosis through the suppression of PI3K/AKT/mTOR/S6K1 pathways and ROS-mediated MAPKs activation. Cancer Lett 312:178–188

    Article  CAS  Google Scholar 

  • Pelicano H, Carney D, Huang P (2004) ROS stress in cancer cells and therapeutic implications. Drug Resist Update 7:97–110

    Article  CAS  Google Scholar 

  • Peters JM (2002) The Anaphase-promoting complex: proteolysis in mitosis and beyond. Mol Cell 9:931–943

    Article  CAS  Google Scholar 

  • Petros JA, Baumann AK, Ruiz-Pesini E, Amin MB, Sun CQ, Hall J, Lim S, Issa MM, Flanders WD, Hosseini SH, Marshall FF, Wallace DC (2005) mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci USA 102:719–724

    Article  CAS  Google Scholar 

  • Piette J, Piret B, Bonizzi G, Schoonbroodt S, Merville MP, Legrand-Poels S, Bours V (1997) Multiple redox regulation in NF-kappaB transcription factor activation. Biol Chem 378:1237–1245

    CAS  Google Scholar 

  • Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S (2004) NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431:461–466

    Article  CAS  Google Scholar 

  • Pilatova M, Varinska L, Perjesi P, Sarissky M, Mirossay L, Solar P, Ostro A, Mojzis J (2010) In vitro antiproliferative and antiangiogenic effects of synthetic chalcone analogues. Toxicol In Vitro 24:1347–1355

    Article  CAS  Google Scholar 

  • Pistritto G, Jost M, Srinivasula SM, Baffa R, Poyet JL, Kari C, Lazebnik Y, Rodeck U, Alnemri ES (2002) Expression and transcriptional regulation of caspase-14 in simple and complex epithelia. Cell Death Differ 9:995–1006

    Article  CAS  Google Scholar 

  • Prasad MNV, Padmalatha K, Jayaram K., Raju NL, Teixeira da Silva J (2007) Medicinal plants from deccan ecoregion, India—traditional knowledge, ethnophamacology, cultivation, utilization, biotechnology and conservation. Med Aromat Plant Sci Biotechnol 1:155–208

  • Pritchard DM, Watson AJ, Potten CS, Jackman AL, Hickman JA (1997) Inhibition by uridine but not thymidine of p53-dependent intestinal apoptosis initiated by 5-fluorouracil: evidence for the involvement of RNA perturbation. Proc Natl Acad Sci USA 94:1795–1799

    Article  CAS  Google Scholar 

  • Qiao Y, Xiang Q, Yuan L, Xu L, Liu Z, Liu X (2013) Herbacetin induces apoptosis in HepG2 cells: involvements of ROS and PI3K/Akt pathway. Food Chem Toxicol 51:426–433

    Article  CAS  Google Scholar 

  • Ramasamy S, Abdul WN, Zainal AN, Manickam S (2013) Effect of extracts from Phyllanthus watsonii Airy Shaw on cell apoptosis in cultured human breast cancer MCF-7 cells. Exp Toxicol Pathol 65:341–349

    Article  CAS  Google Scholar 

  • Rao N (2003) Bioactive phytochemicals in Indian foods and their potential in health promotion and disease prevention. Asia Pac J Clin Nutr 12:9–22

    CAS  Google Scholar 

  • Rao PS, Ramanadham M, Prasad MNV (2009) Anti-proliferative and cytotoxic effects of Strychnos nux-vomicaroot extract on human multiple myeloma cell line—RPMI 8226. Food Chem Toxicol 47:283–288

    Article  CAS  Google Scholar 

  • Ratan RR, Murphy TH, Baraban JM (1994) Rapid Communication: oxidative stress induces apoptosis in embryonic cortical neurons. J Neurochem 62:376–379

    Article  CAS  Google Scholar 

  • Reed JC (1997) Cytochrome C: can’t live with it; can’t live without it. Cell 91:559–562

    Article  CAS  Google Scholar 

  • Ren D, Peng G, Huang H, Wang H, Zhang S (2006) Effect of rhodoxanthin from Potamogeton crispus L. on cell apoptosis in Hela cells. Toxicol In Vitro 20:1411–1418

    Article  CAS  Google Scholar 

  • Rezaei PF, Fouladdel S, Hassani S, Yousefbeyk F, Ghaffari SM, Amin G, Azizi E (2012) Induction of apoptosis and cell cycle arrest by pericarp polyphenol-rich extract of Baneh in human colon carcinoma HT29 cells. Food Chem Toxicol 50:1054–1059

    Article  CAS  Google Scholar 

  • Roya S, Besra SE, De T, Banerjee B, Mukherjee J, Vedasiromoni JR (2008) Induction of apoptosis in human leukemic Cell Lines U937, K562 and HL-60 by Litchi chinensis leaf extract via activation of mitochondria mediated caspase cascades. Open Leukemia J 1:1–14

    Article  Google Scholar 

  • Rubio-Moscardo F, Blesa D, Mestre C, Siebert R, Balasas T, Benito A, Rosenwald A, Climent J, Martinez JI, Schilhabel M, Karran EL, Gesk S, Esteller M, deLeeuw R, Staudt LM, Fernandez-Luna JL, Pinkel D, Dyer MJS, Martinez-Climent JA (2005) Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes. Blood 106:3214–3222

    Article  CAS  Google Scholar 

  • Salvesen GS (2002) Caspases and apoptosis. Essays Biochem 38:9–19

    Article  CAS  Google Scholar 

  • Schnablegger GE, Venables L, Koekemoer TC, Sowemimo AA, Van de Venter M (2013) Cyathula prostrata ethanol extract activates the extrinsic pathway of apoptosis in HeLa and U937 cell lines. South Afr J Bot 88:380–387

    Article  Google Scholar 

  • Schuler M, Green DR (2001) Mechanisms of p53-dependent apoptosis. Biochem Soc Trans 29:684–688

    Article  CAS  Google Scholar 

  • Schumacker PT (2006) Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell 10:175–176

    Article  CAS  Google Scholar 

  • Scorrano L, Oakes SA, Opferman JT, Cheng EH, Pozzan MD, Pozzan T, Korsmeyer SJ (2003) BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science 300:135–139

    Article  CAS  Google Scholar 

  • Sen R, Baltimore D (1986) Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 46:705–716

    Article  CAS  Google Scholar 

  • Sen R, Smale ST (2010) Selectivity of the NF-kB response. Cold Spring Harb Perspect Biol 2:a000257

    Article  CAS  Google Scholar 

  • Seo HJ, Surh YJ (2001) Eupatilin, a pharmacologically active flavone derived from Artemisia plants, induces apoptosis in human promyelocytic leukemia cells. Mutat Res 496:191–198

    Article  CAS  Google Scholar 

  • Seo HS, Choi HS, Kim SR, Choi YK, Woo SM, Shin I, Woo JK, Park SY, Shin YC, Ko SG (2012) Apigenin induces apoptosis via extrinsic pathway, inducing p53 and inhibiting STAT3 and NFκB signaling in HER2-overexpressing breast cancer cells. Mol Cell Biochem 366:319–334

    Article  CAS  Google Scholar 

  • Shang LH, Li CM, Yang ZY, Che DH, Cao JY, Yu Y (2012) Luffa echinata Roxb. induces human colon cancer cell (HT-29) death by triggering the mitochondrial apoptosis pathway. Molecules 17:5780–5794

    Article  CAS  Google Scholar 

  • Shaulian E, Karin M (2001) AP-1 in cell proliferation and survival. Oncogene 20:2390–2400

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Shishodia S, Aggarwal BB (2004) Nuclear factor-kB: a friend or a foe in cancer? Biochem Pharmacol 68:1071–1080

    Article  CAS  Google Scholar 

  • Shu L, Cheung KL, Khor TO, Chen C, Kong AN (2010) Phytochemicals: cancer chemoprevention and suppression of tumor onset and metastasis. Cancer Metastasis Rev 29:483–502

    Article  CAS  Google Scholar 

  • Shukla S, Meeran SM, Katiyar SK (2014) Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention. Cancer Lett 355:9–17

    Article  CAS  Google Scholar 

  • Simon HU, Haj-Yehia A, Levi-Schaffer F (2000) Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 5:415–418

    Article  CAS  Google Scholar 

  • Souza-Fagundes SM, Brumatti G, Martins-Filho OA, Corrêa-Oliveira R, Zani CL, Amarante-Mendes GP (2003) Myriadenolide, a labdane diterpene isolated from Alomia myriadenia (asteraceae) induces depolarization of mitochondrial membranes and apoptosis associated with activation of caspases-8, -9, and -3 in Jurkat and THP-1 cells. Exp Cell Res 290:420–426

    Article  CAS  Google Scholar 

  • Su CC, Chen GW, Tan TW, Lin JG, Chung JG (2006) Crude extract of garlic induced caspase-3 gene expression leading to apoptosis in human colon cancer cells. Vivo 20:85–90

    Google Scholar 

  • Subapriya R, Bhuvaneswari V, Nagini S (2005) Ethanolic neem (Azadirachta indica) leaf extract induces apoptosis in the hamster buccal pouch carcinogenesis model by modulation of Bcl-2, Bim, caspase 8 and caspase 3. Asian Pac J Cancer Prev 6:515–520

    CAS  Google Scholar 

  • Suh J, Rabson AB (2004) NF-kappaB activation in human prostate cancer: important mediator or epiphenomenon? J Cell Biochem 91:100–117

    Article  CAS  Google Scholar 

  • Sun J, McKallip RJ (2011) Plumbagin treatment leads to apoptosis in human K562 leukemia cells through increased ROS and elevated TRAIL receptor expression. Leuk Res 35:1402–1408

    Article  CAS  Google Scholar 

  • Surh YJ (2003) Cancer chemoprevention with dieatary phytochemicals. Nat Rev Cancer 3:768–780

    Article  CAS  Google Scholar 

  • Szatrowski TP, Nathan CF (1991) Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res 51:794–798

    CAS  Google Scholar 

  • Tan G, Gyllenhaal C, Soejarto DD (2006) Biodiversity as a source of anticancer drugs. Curr Drug Targets 7:265–277

    Article  CAS  Google Scholar 

  • Taraphdar AK, Roy M, Bhattacharya RK (2001) Natural products as inducers of apoptosis: implication for cancer therapy and prevention. Curr Sci 80:1387–1396

    CAS  Google Scholar 

  • Thatte U, Dahanukar S (1997) Apoptosis: clinical relevance and pharmacological manipulation. Drugs 54:511–532

    Article  CAS  Google Scholar 

  • Thayyullathil F, Chathoth S, Hago A, Patel M, Galadari S (2008) Rapid reactive oxygen species (ROS) generation induced by curcumin leads to caspase-dependent and -independent apoptosis in L929 cells. Free Radic Biol Med 45:1403–1412

    Article  CAS  Google Scholar 

  • Thippeswamy G, Salimath BP (2007) Induction of caspase-3 activated DNase mediated apoptosis by hexane fraction of Tinospora cordifolia in EAT cells. Environ Toxicol Pharmacol 23:212–220

    Article  CAS  Google Scholar 

  • Trapani JA, Smyth MJ (2002) Functional significance of the perforin/granzyme cell death pathway. Nat Rev Immunol 2:735–747

    Article  CAS  Google Scholar 

  • Tse AKW, Wan CK, Zhua GY, Shen XL, Cheunga HY, Yang M, Fong WF (2007) Magnolol suppresses NF-kB activation and NF-kB regulated gene expression through inhibition of IkappaB kinase activation. Mol Immunol 44:2647–2658

    Article  CAS  Google Scholar 

  • Turrens JF (2003) Mitochondrial formation of reactive oxygen species. J Physiol 552:335–344

    Article  CAS  Google Scholar 

  • Vatansever HS, Sorkun K, Gurhan SID, Ozdal-Kurt F, Turkoz E, Gencay O, Salih B (2010) Propolis from Turkey induces apoptosis through activating caspases in human breast carcinoma cell lines. Acta Histochem 112:546–556

    Article  CAS  Google Scholar 

  • Vercesi AE, Hoffman ME (1993) In: Jones DP, Lash LH (eds) Methods in toxicology. Mitochondrial dysfunction, Schumacker PT. Vol 2, Chapter 21. Academic Press, New York

  • Vermeulen K, Bockstaele DRV, Berneman ZN (2003) The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif 36:131–149

    Article  CAS  Google Scholar 

  • Vogt PK, Bos TJ (1990) JUN: oncogene and transcription factor. Adv Cancer Res 55:1–35

    Article  CAS  Google Scholar 

  • Wajant H (2002) The FAS signaling pathway: more than a paradigm. Science 296:1635–1636

    Article  CAS  Google Scholar 

  • Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS Jr (1998) NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281:1680–1683

    Article  CAS  Google Scholar 

  • Wang Q, Zheng X-L, Yang L, Shi F, Gao Lin-bo, Zhong Ying-jia, Sun H, He F, Lin Y, Wang X (2010) Reactive oxygen species-mediated apoptosis contributes to chemosensitization effect of saikosaponins on cisplatin-induced cytotoxicity in cancer cells. J Exp Clin Cancer Res 29:159

    Article  CAS  Google Scholar 

  • Wang L, Xu ML, Hu JH, Rasmussen SK, Wang MH (2011) Codonopsis lanceolata extract induces G0/G1 arrest and apoptosis in human colon tumor HT-29 cells-involvement of ROS generation and polyamine depletion. Food Chem Toxicol 49:149–154

    Article  CAS  Google Scholar 

  • Whitmarsh AJ, Davis RJ (1996) Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J Mol Med 74:589–607

    Article  CAS  Google Scholar 

  • Won YK, Ong CN, Shi X, Shen HM (2004) Chemopreventive activity of parthenolide against UVB-induced skin cancer and its mechanisms. Carcinogenesis 25:1449–1458

    Article  CAS  Google Scholar 

  • Wu SJ, Chang SP, Lin DL, Wang SS, Hou FF, Ng LT (2009) Supercritical carbon dioxide extract of Physalis peruviana induced cell cycle arrest and apoptosis in human lung cancer H661 cells. Food Chem Toxicol 47:1132–1138

    Article  CAS  Google Scholar 

  • Wyllie AH (1997) Apoptosis: an overview. Br Med Bull 53:451–465

    Article  CAS  Google Scholar 

  • Xiao D, Zeng Y, Prakash L, Badmaev V, Majeed M, Singh SV (2011) Reactive oxygen species-dependent apoptosis by gugulipid extract of ayurvedic medicine plant Commiphora mukul in human prostate cancer cells is regulated by c-Jun N-terminal kinase. Mol Pharmacol 79:499–507

    Article  CAS  Google Scholar 

  • Xu KH, Lu DP (2010) Plumbagin induces ROS-mediated apoptosis in human promyelocytic leukemia cells in vivo. Leuk Res 34:658–665

    Article  CAS  Google Scholar 

  • Xu Y, Ge R, Du J, Xin H, Yi T, Sheng J, Wang Y, Ling C (2009) Corosolic acid induces apoptosis through mitochondrial pathway and caspases activation in human cervix adenocarcinoma HeLa cells. Cancer Lett 284:229–237

    Article  CAS  Google Scholar 

  • Yan Q, Li Y, Jiang Z, Sun Y, Zhu L, Ding Z (2009) Antiproliferation and apoptosis of human tumor cell lines by a lectin (AMML) of Astragalus mongholicus. Phytomedicine 16:586–593

    Article  CAS  Google Scholar 

  • Yen CY, Chiu CC, Haung RW, Yeh CC, Huang KJ, Chang KF, Hseu YC, Chang FR, Chang HW, Wu YC (2012) Antiproliferative effects of goniothalamin on Ca9-22 oral cancer cells through apoptosis, DNA damage and ROS induction. Mutat Res 747:253–258

    Article  CAS  Google Scholar 

  • Yin HQ, Kim YH, Moon CK, Lee BH (2005) Reactive oxygen species-mediated induction of apoptosis by a plant alkaloid 6-methoxydihydrosanguinarine in HepG2 cells. Biochem Pharmacol 70:242–248

    Article  CAS  Google Scholar 

  • Yoo CB, Han KT, Cho KS, Ha J, Park HJ, Nam JH, Kil UH, Lee KT (2005) Eugenol isolated from the essential oil of Eugenia caryophyllata induces a reactive oxygen species-mediated apoptosis in HL-60 human promyelocytic leukemia cells. Cancer Lett 225:41–52

    Article  CAS  Google Scholar 

  • Yu JQ, Yin Y, Lei JC, Zhang XQ, Chen W, Ding CL, Wu S, He XY, Liu YW, Zou GL (2012) Activation of apoptosis by ethyl acetate fraction of ethanol extract of Dianthus superbus in HepG2 cell line. Cancer Epidemiol 36:e40–e45

    Article  Google Scholar 

  • Yuan J, Shaham S, Ledoux HM, Horvitz HR (1993) The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-b-converting enzyme. Cell 75:641–652

    Article  CAS  Google Scholar 

  • Zangar RC, Davydov DR, Verma S (2004) Mechanisms that regulate production of reactive oxygen species by cytochrome P450. Toxicol Appl Pharmacol 199:316–331

    Article  CAS  Google Scholar 

  • Zarnegar B, He JQ, Oganesyan G, Hoffmann A, Baltimore D, Cheng G (2004) Unique CD40-mediated biological program in B cell activation requires both type 1 and type 2 NF-kappaB activation pathways. Proceedings of the National Academy of Sciences USA 101:8108–8113

    Article  CAS  Google Scholar 

  • Zarnegar BJ, Wang Y, Mahoney DJ, Dempsey PW, Cheung HH, He J, Shiba T, Yang X, Yeh WC, Mak TW (2008) Noncanonical NF-kappaB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK. Nat Immunol 9:1371–1378

    Article  CAS  Google Scholar 

  • Zeng YW, Liu XZ, Lv ZC, Peng YH (2012) Effects of Ficus hirta Vahl. (Wuzhimaotao) extracts on growth inhibition of HeLa cells. Exp Toxicol Pathol 64:743–749

    Article  Google Scholar 

  • Zhang Y, Tang LI (2007) Discovery and development of sulforaphane as a cancer chemopreventive phytochemical. Acta Pharmacol Sin 28:1343–1354

    Article  CAS  Google Scholar 

  • Zhuang WJ, Fong CC, Cao J, Ao L, Leung CH, Cheung HY, Xiao PG, Fong WF, Yang MS (2004) Involvement of NF-[kappa]B and c-myc signaling pathways in the apoptosis of HL-60 cells induced by alkaloids of Tripterygium hypoglaucum (levl.) Hutch. Phytomedicine 11:295–302

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by the Council of Scientific and Industrial Research (CSIR) [38(1265)/10/EMR-II], New Delhi (India) and the UPE programme of University Grants Commission (UGC), New Delhi (India).

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  1. Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, 143005, Punjab, India

    Manish Kumar, Varinder Kaur & Satwinderjeet Kaur

  2. Department of Chemistry, UGC Centre for Advanced Studies, Guru Nanak Dev University, Amritsar, 143005, Punjab, India

    Subodh Kumar

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Kumar, M., Kaur, V., Kumar, S. et al. Phytoconstituents as apoptosis inducing agents: strategy to combat cancer. Cytotechnology 68, 531–563 (2016). https://doi.org/10.1007/s10616-015-9897-2

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