Skip to main content

Insight Approaches of Medicinal Plants for the Discovery of Anticancer Drugs

  • Chapter
  • First Online:
Anticancer Plants: Clinical Trials and Nanotechnology

Abstract

Cancer is one of the most serious illnesses of our civilization. The International Agency for Research on Cancer estimated that 14.1 million new cancer cases were diagnosed and that 8.2 million patients died from this disease worldwide in 2012 alone. Therefore, there is an urgent need for novel anticancer agents as well as new treatment strategies. Natural products have been valuable sources of new therapeutic agents. Thus, the aim of present chapter is to provide an overview of the anticancer natural compounds highlighting the successful cases with clinical application such as Taxol, vincristine and omacetaxine mepesuccinate; those involved in clinical trials such as parthenolide, betulinic acid, ingenol mebutate and curcumin; and the ones with high degree of activity and safety profile such as resveratrol, ursolic acid, tetrandrine and triptolide. For each one of these compounds, it will be presented and discussed its natural origin, cell target, mechanism of action, pharmacologic aspects as well as the structural modifications that improve its anticancer properties in order to summarize the recent medicinal advances of natural anticancer compounds and their analogues. All these aspects aim to draw our readers’ attention to the plants and/or their secondary metabolites therapeutic potential and in consequence value the plants’ role in anticancer drug discovery.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

  • Adetutu A, Morgan WA, Corcoran O (2011) Ethnopharmacological survey and in vitro evaluation of wound-healing plants used in South-western Nigeria. J Ethnopharmacol 137:50–56

    Article  PubMed  Google Scholar 

  • Adio AM (2009) Germacrenes A-E and related compounds: thermal, photochemical and acid induced transannular cyclizations. Tetrahedron 65:1533–1552

    Article  CAS  Google Scholar 

  • Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y (2004) Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res 24:2783–2840

    CAS  PubMed  Google Scholar 

  • Ahmed I, Roy BC, Subramaniam D, Ganie SA, Kwatra D, Dixon D, Anant S, Zargar MA, Umar S (2016) An ornamental plant targets epigenetic signaling to block cancer stem cell-driven colon carcinogenesis. Carcinogenesis 37:385–396

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Akard L, Kantarjian HM, Nicolini FE, Wetzler M, Lipton JH, Baccarani M, Jean Khoury H, Kurtin S, Li E, Munteanu M, Cortes J (2016) Incidence and management of myelosuppression in patients with chronic- and accelerated-phase chronic myeloid leukemia treated with omacetaxine mepesuccinate. Leuk Lymphoma 57:654–665

    Article  CAS  PubMed  Google Scholar 

  • Alamolhodaei NS, Tsatsakis AM, Ramezani M, Hayes AW, Karimi G (2017) Resveratrol as MDR reversion molecule in breast cancer: an overview. Food Chem Toxicol 103:223–232

    Article  CAS  PubMed  Google Scholar 

  • Ali F, Rahul, Naz F, Jyoti S, Siddique YH (2017a) Health functionality of apigenin: a review. Int J Food Prop 20:1197–1238

    Article  CAS  Google Scholar 

  • Ali MTM, Zahari H, Aliasak A, Lim SM, Ramasamy K, Macabeoacabeo APG (2017b) Synthesis, characterization and cytotoxic activity of betulinic acid and sec-betulinic acid derivatives against human colorectal carcinoma. Orient J Chem 33:242–248

    Article  CAS  Google Scholar 

  • Ali-Seyed M, Jantan I, Vijayaraghavan K, Bukhari SN (2016) Betulinic acid: recent advances in chemical modifications, effective delivery, and molecular mechanisms of a promising anticancer therapy. Chem Biol Drug Des 87:517–536

    Article  CAS  PubMed  Google Scholar 

  • Aljuffali IA, Fang CL, Chen CH, Fang JY (2016) Nanomedicine as a strategy for natural compound delivery to prevent and treat cancers. Curr Pharm Des 22:4219–4231

    Article  CAS  PubMed  Google Scholar 

  • Allam S, Moharam M, Alarfaj G (2014) Assessing patients preference for integrating herbal medicine within primary care services in Saudi Arabia. J Evid-Based Compl Altern Med 19:205–210

    Article  Google Scholar 

  • Allegra A, Innao V, Russo S, Gerace D, Alonci A, Musolino C (2017) Anticancer activity of curcumin and its analogues: preclinical and clinical studies. Cancer Investig 35:1–22

    Article  CAS  Google Scholar 

  • Alonso-Castro AJ, Villarreal ML, Salazar-Olivo LA, Gomez-Sanchez M, Dominguez F, Garcia-Carranca A (2011) Mexican medicinal plants used for cancer treatment: pharmacological, phytochemical and ethnobotanical studies. J Ethnopharmacol 133:945–972

    Article  CAS  PubMed  Google Scholar 

  • Alsaied OA, Sangwan V, Banerjee S, Krosch TC, Chugh R, Saluja A, Vickers SM, Jensen EH (2014) Sorafenib and triptolide as combination therapy for hepatocellular carcinoma. Surgery 156:270–279

    Article  PubMed  Google Scholar 

  • Antônio E, Junior ORA, de Araújo IS, Khalil NM, Mainardes RM (2017) Poly(lactic acid) nanoparticles loaded with ursolic acid: characterization and in vitro evaluation of radical scavenging activity and cytotoxicity. Mater Sci Eng C 71:156–166

    Article  CAS  Google Scholar 

  • Aziato L, Odai PNA (2016) Exploring the safety and clinical use of herbal medicine in the contemporary Ghanaian context: a descriptive qualitative study. J Herb Med 8:62–67

    Article  Google Scholar 

  • Banerjee S, Saluja A (2015) Minnelide, a novel drug for pancreatic and liver cancer. Pancreatology 15:39–43

    Article  CAS  Google Scholar 

  • Baranello MP, Bauer L, Jordan CT, Benoit DSW (2015) Micelle delivery of parthenolide to acute myeloid leukemia cells. Cell Mol Bioeng 8:455–470

    Article  PubMed  CAS  Google Scholar 

  • Barbuti AM, Chen ZS (2015) Paclitaxel through the ages of anticancer therapy: exploring its role in chemoresistance and radiation therapy. Cancers 7:2360–2371

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Basmadjian C, Zhao Q, Bentouhami E, Djehal A, Nebigil CG, Johnson RA, Serova M, de Gramont A, Faivre S, Raymond E, Désaubry LG (2014) Cancer wars: natural products strike back. Front Chem 2:20. https://doi.org/10.3389/fchem.2014.00020

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ben-Arye E, Mahajna J, Aly R, Ali-Shtayeh MS, Bentur Y, Lev E, Deng G, Samuels N (2016) Exploring an herbal “wonder cure” for cancer: a multidisciplinary approach. J Cancer Res Clin Oncol 142:1499–1508

    Article  PubMed Central  PubMed  Google Scholar 

  • Benhadji KA, Serova M, Ghoul A, Cvitkovic E, Le Tourneau C, Ogbourne SM, Lokiec F, Calvo F, Hammel P, Faivre S, Raymond E (2008) Antiproliferative activity of PEP005, a novel ingenol angelate that modulates PKC functions, alone and in combination with cytotoxic agents in human colon cancer cells. Br J Cancer 99:1808–1815

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Berman B (2015) Safety and tolerability of ingenol mebutate in the treatment of actinic keratosis. Exp Opin Drug Saf 14:1969–1978

    Article  CAS  Google Scholar 

  • Bernabeu E, Cagel M, Lagomarsino E, Moretton M, Chiappetta DA (2017) Paclitaxel: what has been done and the challenges remain ahead. Int J Pharm 526:474–495

    Article  CAS  PubMed  Google Scholar 

  • Bhandary MJ, Chandrashekar KR, Kaveriappa KM (1995) Medical ethnobotany of the Siddis of Uttara Kannada district, Karnataka, Indian. J Ethnopharm 47:149–158

    Article  CAS  Google Scholar 

  • Bhanot A, Sharma R, Noolvi MN (2011) Natural sources as potential anticancer agents: a review. Int J Phytomed 3:9–26

    Google Scholar 

  • Bisht K, Wagner KH, Bulmer AC (2010) Curcumin, resveratrol and flavonoids as anti-inflammatory, cyto- and DNA-protective dietary compounds. Toxicology 278:88–100

    Article  CAS  PubMed  Google Scholar 

  • Borges GÁ, Rêgo DF, Assad DX, Coletta RD, De Luca CG, Guerra EN (2017) In vivo and in vitro effects of curcumin on head and neck carcinoma: a systematic review. J Oral Pathol Med 46:3–20

    Google Scholar 

  • Boutennoun H, Boussouf L, Rawashdeh A, Al-Qaoud K, Abdelhafez S, Kebieche M, Madani K (2017) In vitro cytotoxic and antioxidant activities of phenolic components of Algerian Achillea odorata leaves. Arab J Chem 10:403–409

    Article  CAS  Google Scholar 

  • Bridgeman BB, Wang P, Ye B, Pelling JC, Volpert OV, Tong X (2016) Inhibition of mTOR by apigenin in UVB-irradiated keratinocytes: a new implication of skin cancer prevention. Cell Signal 28:460–468

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Brufsky A (2017) nab-Paclitaxel for the treatment of breast cancer: an update across treatment settings. Exp Hematol Oncol 6:7. https://doi.org/10.1186/s40164-017-0066-5

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Burns J, Yokota T, Ashihara H, Lean MEJ, Crozier A (2002) Plant foods and herbal sources of resveratrol. J Agric Food Chem 50:3337–3340

    Article  CAS  PubMed  Google Scholar 

  • Buyuklu M, Kandemir FM, Ozkaraca TM, Bakirci EM, Topal E (2014) Protective effect of curcumin against contrast induced nephropathy in rat kidney: what is happening to oxidative stress, inflammation, autophagy and apoptosis. Eur Rev Med Pharmacol Sci 18:461–470

    CAS  PubMed  Google Scholar 

  • Carlisi D, Buttitta G, Di Fiore R, Scerri C, Drago-Ferrante R, Vento R, Tesoriere G (2016) Parthenolide and DMAPT exert cytotoxic effects on breast cancer stem-like cells by inducing oxidative stress, mitochondrial dysfunction and necrosis. Cell Death Dis 7:e2194. https://doi.org/10.1038/cddis.2016.94

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Chainani-Wu N (2003) Safety and anti-inflammatory activity of curcumin: a component of turmeric (Curcuma longa). J Altern Complement Med 9:161–168

    Article  PubMed  Google Scholar 

  • Chan SF, Chen YY, Lin JJ, Liao CL, Ko YC, Tang NY, Kuo CL, Liu KC, Chung JG (2017) Triptolide induced cell death through apoptosis and autophagy in murine leukemia WEHI-3 cells in vitro and promoting immune responses in WEHI-3 generated leukemia mice in vivo. Environ Toxicol 32:550–568

    Article  CAS  PubMed  Google Scholar 

  • Chang Y, Meng FC, Wang R, Wang CM, Lu XY, Zhang QW (2017) Chemistry, bioactivity, and the structure-activity relationship of cephalotaxine-type alkaloids from Cephalotaxus sp. In: Atta-ur-Rahman FRS (ed) Studies in natural products chemistry. Elsevier Science Publishers, Amsterdam, pp 339–373

    Google Scholar 

  • Chen J, Li W, Yao H, Xu J (2015) Insights into drug discovery from natural products through structural modification. Fitoterapia 103:231–241

    Article  CAS  PubMed  Google Scholar 

  • Chen J, He ZM, Wang FL, Zhang ZS, Liu XZ, Zhai DD, Chen WD (2016) Curcumin and its promise as an anticancer drug: an analysis of its anticancer and antifungal effects in cancer and associated complications from invasive fungal infections. Eur J Pharmacol 772:33–42

    Article  CAS  PubMed  Google Scholar 

  • Chen QZ, Li Y, Shao Y, Zeng YH, Ren WY, Liu RX, Zhou LY, Hu XL, Huang M, He F, Sun WJ, Wu K, He BC (2017) TGF-β1/PTEN/PI3K signaling plays a critical role in the anti-proliferation effect of tetrandrine in human colon cancer cells. Int J Oncol 50:1011–1021

    Article  CAS  PubMed  Google Scholar 

  • Chinembiri TN, du Plessis LH, Gerber M, Hamman JH, du Plessis J (2014) Review of natural compounds for potential skin cancer treatment. Molecules 19:11679–11721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chiu CH, Chou YC, Lin JP, Kuo CL, Lu HF, Huang YP, Yu CC, Lin ML, Chung JG (2015) Chloroform extract of Solanum lyratum induced G0/G1 arrest via p21/p16 and induced apoptosis via reactive oxygen species, caspases and mitochondrial pathways in human oral cancer cell lines. Am J Chin Med 43:1453–1469

    Article  CAS  PubMed  Google Scholar 

  • Chudzik M, Korzonek-Szlacheta I, Król W (2015) Triterpenes as potentially cytotoxic compounds. Molecules 20:1610–1625. https://doi.org/10.3390/molecules20011610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chugh R, Sangwan V, Patil SP, Dudeja V, Dawra RK, Banerjee S, Schumacher RJ, Blazar BR, Georg GI, Vickers SM, Saluja AK (2012) A preclinical evaluation of minnelide as a therapeutic agent against pancreatic cancer. Sci Transl Med 4:156ra139. https://doi.org/10.1126/scitranslmed.3004334

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Chung C (2014) Omacetaxine for treatment-resistant or treatment-intolerant adult chronic myeloid leukemia. Am J Health Syst Pharm 71:279–288

    Article  CAS  PubMed  Google Scholar 

  • Collier NJ, Ali FR, Lear JT (2014) Ingenol mebutate: a novel treatment for actinic keratosis. Clin Pract 11:295–306

    Article  CAS  Google Scholar 

  • Cortes JE, Kantarjian HM, Rea D, Wetzler M, Lipton JH, Akard L, Khoury HJ, Michallet M, Guerci-Bresler A, Chuah C, Hellmann A, Digumarti R, Parikh PM, Legros L, Warzocha K, Baccarani M, Li E, Munteanu M, Nicolini FE (2015) Final analysis of the efficacy and safety of omacetaxine mepesuccinate in patients with chronic or accelerated-phase chronic myeloid leukemia: results with 24 months of follow-up. Cancer 121:1637–1644

    Article  PubMed  CAS  Google Scholar 

  • Cottart CH, Nivet-Antoine V, Beaudeux JL (2014) Review of recent data on the metabolism, biological effects, and toxicity of resveratrol in humans. Mol Nutr Food Res 58:7–21

    Article  CAS  PubMed  Google Scholar 

  • Csuk R, Schmuck K, Schäfer R (2006) A practical synthesis of betulinic acid. Tetrahedron Lett 47:8769–8770

    Article  CAS  Google Scholar 

  • Czyz M, Koprowska K, Sztiller-Sikorska M (2013) Parthenolide reduces the frequency of ABCB5-positive cells and clonogenic capacity of melanoma cells from anchorage independent melanospheres. Cancer Biol Ther 14:135–145

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • D’Anneo A, Carlisi D, Lauricella M, Puleio R, Martinez R, Di Bella S, Di Marco P, Emanuele S, Di Fiore R, Guercio A, Vento R, Tesoriere G (2013) Parthenolide generates reactive oxygen species and autophagy in MDA-MB231 cells. A soluble parthenolide analogue inhibits tumour growth and metastasis in a xenograft model of breast cancer. Cell Death Dis 4:e891. https://doi.org/10.1038/cddis.2013.415

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Dadgar S, Ramjan Z, Floriano WB (2013) Paclitaxel is an inhibitor and its boron dipyrromethene derivative is a fluorescent recognition agent for botulinum neurotoxin subtype A. J Med Chem 56:2791–2803

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Damlaj M, Lipton JH, Assouline SE (2016) A safety evaluation of omacetaxine mepesuccinate for the treatment of chronic myeloid leukemia. Exp Opin Drug Saf 15:1279–1286

    Article  CAS  Google Scholar 

  • Das A, Dhanjal JK (2015) Medicinal plants, a gold mine of anticancer compounds. Am Int J Res Formal Appl Nat Sci 9:14–23

    Google Scholar 

  • Das C, Mishra P, Das D, Maharana L, Ghosh G (2015) Development of quality control parameters for standardization of Triumfetta rhomboidea. Int J Pharmacol Phytochem Res 7:934–942

    Google Scholar 

  • Dasiram JD, Ganesan R, Kannan J, Kotteeswaran V, Sivalingam N (2017) Curcumin inhibits growth potential by G1 cell cycle arrest and induces apoptosis in p53-mutated COLO 320DM human colon adenocarcinoma cells. Biomed Pharmacother 86:373–380

    Article  CAS  PubMed  Google Scholar 

  • Deng Y, Verron E, Rohanizadeh R (2016) Molecular mechanisms of anti-metastatic activity of curcumin. Anticancer Res 36:5639–5647

    Article  CAS  PubMed  Google Scholar 

  • Deogade SC, Ghate S (2015) Curcumin: therapeutic applications in systemic and oral health. Int J Biol Pharma Res 6:281–290

    Article  CAS  Google Scholar 

  • Dianhar H, Syah YM, Mujahidin D, Hakim EH, Juliawaty LD (2014) A flavone derivative from Sesbania sesban leaves and its cytotoxicity against murine leukemia P-388 cells. AIP Conf Proc 1589:411–413

    Article  CAS  Google Scholar 

  • Dias DA, Urban S, Roessner U (2012) A historical overview of natural products in drug discovery. Metabolites 2:303–336

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Doan HQ, Gulati N, Levis WR (2012) Ingenol mebutate: potential for further development of cancer immunotherapy. J Drugs Dermatol 11:1156–1157

    PubMed Central  PubMed  CAS  Google Scholar 

  • Drury (1991) Plants and wart cures in England from the seventeenth to the nineteenth century: some examples. Folklore 102:97–100

    Article  Google Scholar 

  • Duan R, Tian F, Sun J (2016) Structural basis and energy landscape of apigenin-induced cancer cell apoptosis mechanism in PI3K/Akt pathway. Mol Simul 42:138–148

    Article  CAS  Google Scholar 

  • Duhem N, Danhier F, Préat V (2014) Vitamin E-based nanomedicines for anticancer drug delivery. J Control Release 182:33–44

    Article  CAS  PubMed  Google Scholar 

  • Enioutina EY, Salis ER, Job KM, Gubarev MI, Krepkova LV, Sherwin CM (2017) Herbal medicines: challenges in the modern world. Part 5. Status and current directions of complementary and alternative herbal medicine worldwide. Exp Rev Clin Pharmacol 10:327–338

    Article  CAS  Google Scholar 

  • Erdogan S, Doganlar O, Doganlar ZB, Serttas R, Turkekul K, Dibirdik I, Bilir A (2016) The flavonoid apigenin reduces prostate cancer CD44+ stem cell survival and migration through PI3K/Akt/NF-κB signalling. Life Sci 162:77–86

    Article  CAS  PubMed  Google Scholar 

  • Erdogan S, Turkekul K, Serttas R, Erdogan Z (2017) The natural flavonoid apigenin sensitizes human CD44+ prostate cancer stem cells to cisplatin therapy. Biomed Pharmacother 88:210–217

    Article  CAS  PubMed  Google Scholar 

  • Fabricant DS, Farnsworth NR (2001) The value of plants used in traditional medicine for drug discovery. Environ Health Perspect 109:69–75

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Fonrose X, Ausseil F, Soleilhac E, Masson V, David B, Pouny I, Cintrat J-C, Rousseau B, Barette C, Massiot G, Lafanechère L (2007) Parthenolide inhibits tubulin carboxypeptidase activity. Cancer Res 67:3371–3378

    Article  CAS  PubMed  Google Scholar 

  • Formagio AS, Vieira MC, Volobuff CR, Silva MS, Matos AI, Cardoso CA, Foglio MA, Carvalho JE (2015) In vitro biological screening of the anticholinesterase and antiproliferative activities of medicinal plants belonging to Annonaceae. Braz J Med Biol Res 48:308–315

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Fu Z, Chen X, Guan S, Yan Y, Lin H, Hua ZC (2015) Curcumin inhibits angiogenesis and improves defective hematopoiesis induced by tumor-derived VEGF in tumor model through modulating VEGF-VEGFR2 signaling pathway. Oncotarget 6:19469–19482

    PubMed Central  PubMed  Google Scholar 

  • Gali-Muhtasib H, Hmadi R, Kareh M, Tohme R, Darwiche N (2015) Cell death mechanisms of plant-derived anticancer drugs: beyond apoptosis. Apoptosis 20:1531–1562

    Article  CAS  PubMed  Google Scholar 

  • Gallego A, Malik S, Yousefzadi M, Makhzoum A, Tremouillaux-Guiller J, Bonfill M (2017) Taxol from Corylus avellana: paving the way for a new source of this anticancer drug. Plant Cell Tissue Organ Cult 129:1–16

    Article  CAS  Google Scholar 

  • Gao Y, Jia ZL, Kong XY, Li Q, Chang DZ, Wei DY, Le XD, Huang SD, Huang SY, Wang LW, Xie KP (2011) Combining betulinic acid and mithramycin a effectively suppresses pancreatic cancer by inhibiting proliferation, invasion, and angiogenesis. Cancer Res 71:5182–5193

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Genova C, Alama A, Coco S, Rijavec E, Dal Bello MG, Vanni I, Biello F, Barletta G, Rossi G, Grossi F (2016) Vinflunine for the treatment of non-small cell lung cancer. Exp Opin Invest Drugs 25:1447–1455

    Article  CAS  Google Scholar 

  • Ghantous A, Sinjab A, Herceg Z, Darwiche N (2013) Parthenolide: from plant shoots to cancer roots. Drug Discov Today 18:894–905

    Article  CAS  PubMed  Google Scholar 

  • Gheorgheosu D, Duicu O, Dehelean C, Soica C, Muntean D (2014) Betulinic acid as a potent and complex antitumor phytochemical: a minireview. Anti Cancer Agents Med Chem 14:936–945

    Article  CAS  Google Scholar 

  • Gidding CE, Kellie SJ, Kamps WA, de Graaf SS (1999) Vincristine revisited. Crit Rev Oncol Hematol 29:267–287

    Article  CAS  PubMed  Google Scholar 

  • Giddings LA, Newman DJ (2013) Microbial natural products: molecular blueprints for antitumor drugs. J Indian Microbiol Biotechnol 40:1181–1210

    Article  CAS  Google Scholar 

  • Gill KK, Kamal MM, Kaddoumi A, Nazzal S (2016) EGFR targeted delivery of paclitaxel and parthenolide co-loaded in PEG-Phospholipid micelles enhance cytotoxicity and cellular uptake in non-small cell lung cancer cells. J Drug Deliv Sci Technol 36:150–155

    Article  CAS  Google Scholar 

  • Gong X, Chen Y, Wu Y (2015) Absorption and metabolism characteristics of triptolide as determined by a sensitive and reliable LC-MS/MS method. Molecules 20:8928–8940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gotta H, Adolf W, Opferkuch HJ, Hecker E (1984) On the active principles of the Euphorbiaceae IX. Ingenane type diterpene esters from 5 Euphorbia species. Z Naturforsch Sect B 39:683–694

    Article  Google Scholar 

  • Graham JG, Quinn ML, Fabricant DS, Farnsworth NR (2000) Plants used against cancer – an extension of the work of Jonathan Hartwell. J Ethnopharmacol 73:347–377

    Article  CAS  PubMed  Google Scholar 

  • Guerram M, Jiang ZZ, Sun L, Zhu X, Zhang LY (2015) Antineoplastic effects of deoxypodophyllotoxin, a potent cytotoxic agent of plant origin, on glioblastoma U-87 MG and SF126 cells. Pharmacol Rep 67:245–252

    Article  CAS  PubMed  Google Scholar 

  • Gunn EJ, Williams JT, Huynh DT, Iannotti MJ, Han C, Barrios FJ, Kendall S, Glackin CA, Colby DA, Kirshner J (2011) The natural products parthenolide and andrographolide exhibit anticancer stem cell activity in multiple myeloma. Leuk Lymph 52:1085–1097

    Article  CAS  Google Scholar 

  • Gupta S, Pramanik D (2016) Phytochemicals and cancer stem cells: a pancreatic cancer overview. Curr Chem Biol 10:98–108

    Article  CAS  Google Scholar 

  • Gupta SC, Patchva S, Aggarwal BB (2013) Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J 15:195–218

    Article  CAS  PubMed  Google Scholar 

  • Habli Z, Toumieh G, Fatfat M, Rahal ON, Gali-Muhtasib H (2017) Emerging cytotoxic alkaloids in the battle against cancer: overview of molecular mechanisms. Molecules 22:E250. https://doi.org/10.3390/molecules22020250

    Article  CAS  PubMed  Google Scholar 

  • Haris P, Mary V, Aparna P, Dileep KV, Sudarsanakumar C (2017) A comprehensive approach to ascertain the binding mode of curcumin with DNA. Spectrochim Acta A 175:155–163

    Article  CAS  Google Scholar 

  • Hatcher H, Planalp R, Cho J, Torti FM, Torti SV (2008) Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci 65:1631–1652

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • He YC, Zhou FL, Shen Y, Liao DF, Cao D (2014) Apoptotic death of cancer stem cells for cancer therapy. Int J Mol Sci 15:8335–8351

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Heiblig M, Sobh M, Nicolini FE (2014) Subcutaneous omacetaxine mepesuccinate in patients with chronic myeloid leukemia in tyrosine kinase inhibitor-resistant patients: review and perspectives. Leuk Res 38:1145–1153

    Article  CAS  PubMed  Google Scholar 

  • Hexum JK, Becker CM, Kempema AM, Ohlfest JR, Largaespada DA, Harki DA (2015) Parthenolide prodrug LC-1 slows growth of intracranial glioma. Bioorg Med Chem Lett 25:2493–2495

    Article  CAS  PubMed  Google Scholar 

  • Holonec L, Ranga F, Crainic D, Truţa A, Socaciu C (2012) Evaluation of betulin and betulinic acid content in birch bark from different forestry areas of western carpathians. Not Bot Hortic Agrobot 40:99–105

    Article  CAS  Google Scholar 

  • Hu S, Zhou Q, Wu WR, Duan YX, Gao ZY, Li YW, Lu Q (2016) Anticancer effect of deoxypodophyllotoxin induces apoptosis of human prostate cancer cells. Oncol Lett 12:2918–2923

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Huang D, Li Y, Cui F, Chen J, Sun J (2016) Purification and characterization of a novel polysaccharide-peptide complex from Clinacanthus nutans Lindau leaves. Carbohydr Polym 137:701–708

    Article  CAS  PubMed  Google Scholar 

  • Imran M, Ullah A, Saeed F, Nadeem M, Arshad MU, Suleria HAR (2016) Cucurmin; anticancer and antitumor perspectives – a comprehensive review. Crit Rev Food Sci Nutr 22:1–23

    Google Scholar 

  • Isah T (2016) Anticancer alkaloids from trees: development into drugs. Pharmacogn Rev 10:90–99

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Isharwal S, Modi S, Arora N, Uhlrich C, Giri B, Barlass U, Soubra A, Chugh R, Dehm SM, Dudeja V, Saluja A, Banerjee S, Konety B (2017) Minnelide inhibits androgen dependent, castration resistant prostate cancer growth by decreasing expression of androgen receptor full length and splice variants. Prostate 77:584–596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iweala EEJ, Liu FF, Cheng RR, Li Y, Omonhinmin CA, Zhang YJ (2015) Anticancer and free radical scavenging activity of some Nigerian food plants in vitro. Int J Cancer Res 11:41–51

    Article  CAS  Google Scholar 

  • Jain P, Gulati S, Seth R, Bakhshi S, Toteja GS, Pandey RM (2014) Vincristine-induced neuropathy in childhood ALL (acute lymphoblastic leukemia) survivors: prevalence and electrophysiological characteristics. J Child Neur 29:932–937

    Article  Google Scholar 

  • Jain S, Dwivedi J, Jain PK, Satpathy S, Patra A (2016) Medicinal plants for treatment of cancer: a brief review. Pharm J 8:87–101

    CAS  Google Scholar 

  • Jannet SB, Hymery N, Bourgou S, Jdey A, Lachaal M, Magné C, Ksouri R (2017) Antioxidant and selective anticancer activities of two Euphorbia species in human acute myeloid leukemia. Biomed Pharmacother 90:375–385

    Article  CAS  PubMed  Google Scholar 

  • Jeyamohan S, Moorthy RK, Kannan MK, Arockiam AJV (2016) Parthenolide induces apoptosis and autophagy through the suppression of PI3K/Akt signaling pathway in cervical cancer. Biotechnol Lett 38:1251–1260

    Article  CAS  PubMed  Google Scholar 

  • Jiang Z, Wu M, Miao J, Duan H, Zhang S, Chen M, Sun L, Wang Y, Zhang X, Zhu X, Zhang L (2013) Deoxypodophyllotoxin exerts both anti-angiogenic and vascular disrupting effects. Int J Biochem Cell Biol 45:1710–1719

    Article  CAS  PubMed  Google Scholar 

  • Jordan BC, Mock CD, Thilagavathi R, Selvam C (2016) Molecular mechanisms of curcumin and its semisynthetic analogues in prostate cancer prevention and treatment. Life Sci 152:135–144

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Jørgensen L, McKerrall SJ, Kuttruff CA, Ungeheuer F, Felding J, Baran PS (2013) 14-step synthesis of (+)-ingenol from (+)-3-carene. Science 341:878–882

    Article  CAS  PubMed  Google Scholar 

  • Jung GR, Kim KJ, Choi CH, Lee TB, Han SI, Han HK, Lim SC (2007) Effect of betulinic acid on anticancer drug-resistant colon cancer cells. Basic Clin Pharmacol Toxicol 101:277–285

    Article  CAS  PubMed  Google Scholar 

  • Kamau LN, Mbaabu MP, Mbaria JM, Karuri GP, Kiama SG (2016) Knowledge and demand for medicinal plants used in the treatment and management of diabetes in Nyeri County, Kenya. J Ethnopharmacol 189:218–229

    Article  PubMed  Google Scholar 

  • Katz L, Baltz RH (2016) Natural product discovery: past, present and future. J Indian Microbiol Biotechnol 43:155–176

    Article  CAS  Google Scholar 

  • Kedei N (2004) Characterization of the interaction of ingenol 3-angelate with protein kinase C. Cancer Res 64:3243–3255

    Article  PubMed  CAS  Google Scholar 

  • Khaled M, Jiang ZZ, Zhang LY (2013) Deoxypodophyllotoxin: a promising therapeutic agent from herbal medicine. J Ethnopharmacol 149:24–34

    Article  CAS  PubMed  Google Scholar 

  • Khalid EB, Ayman E-ME-K, Rahman H, Abdelkarim G, Najda A (2016) Natural products against cancer angiogenesis. Tumor Biol 37:14513–14536

    Article  CAS  Google Scholar 

  • Khan IN, Al-Karim S, Bora RS, Chaudhary AG, Saini KS (2015) Cancer stem cells: a challenging paradigm for designing targeted drug therapies. Drug Discov Today 20:1205–1216

    Article  PubMed  CAS  Google Scholar 

  • Khanna C, Rosenberg M, Vail DM (2015) A review of paclitaxel and novel formulations including those suitable for use in dogs. J Vet Intern Med 29:1006–1012

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kim G (2017) nab-paclitaxel for the treatment of pancreatic cancer. Cancer Manag Res 9:85–96

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kim ES, Moon A (2015) Ursolic acid inhibits the invasive phenotype of SNU-484 human gastric cancer cells. Oncol Lett 9:897–902

    Article  PubMed  Google Scholar 

  • Kim SL, Kim SH, Trang KTT, Kim IH, Lee SO, Lee ST, Kim DG, Kang SB, Kim SW (2013) Synergistic antitumor effect of 5-fluorouracil in combination with parthenolide in human colorectal cancer. Cancer Lett 335:479–486

    Article  CAS  PubMed  Google Scholar 

  • Kim SH, Kang JG, Kim CS, Ihm SH, Choi MG, Yoo HJ, Lee SJ (2016) Synergistic cytotoxicity of BIIB021 with triptolide through suppression of PI3K/Akt/mTOR and NF-κB signal pathways in thyroid carcinoma cells. Biomed Pharmacother 83:22–32

    Article  CAS  PubMed  Google Scholar 

  • Kim SL, Kim SH, Park YR, Liu YC, Kim EM, Jeong H-J, Kim YN, Seo SY, Kim IH, Lee SO, Lee ST, Kim SW (2017) Combined parthenolide and balsalazide have enhanced antitumor efficacy through blockade of NF-kB activation. Mol Cancer Res 15:141–151

    Article  CAS  PubMed  Google Scholar 

  • Kinch MS, Haynesworth A, Kinch SL, Hoyer D (2014) An overview of FDA-approved new molecular entities: 1827–2013. Drug Discov Today 19:1033–1039

    Article  CAS  PubMed  Google Scholar 

  • King AE, Southam KA, Dittmann J, Vickers JC (2013) Excitotoxin-induced caspase-3 activation and microtubule disintegration in axons is inhibited by taxol. Acta Neuropathol Commun 1:59. https://doi.org/10.1186/2051-5960-1-59

    Article  PubMed Central  PubMed  Google Scholar 

  • Klinger NV, Mittal S (2016) Therapeutic potential of curcumin for the treatment of brain tumors. Oxi Med Cell Long 2016:9324085. https://doi.org/10.1155/2016/9324085

    Article  CAS  Google Scholar 

  • Klippstein R, Bansal SS, Al-Jamal KT (2016) Doxorubicin enhances curcumin’s cytotoxicity in human prostate cancer cells in vitro by enhancing its cellular uptake. Int J Pharma 514:169–175

    Article  CAS  PubMed  Google Scholar 

  • Kocaadam B, Sanlier N (2017) Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. Crit Rev Food Sci Nutr 57:2889–2895

    Article  CAS  PubMed  Google Scholar 

  • Koduru S, Grierson DS, van de Venter M, Afolayan AJ (2007) Anticancer activity of steroid alkaloids isolated from Solanum aculeastrum. Pharm Biol 45:613–618

    Article  CAS  Google Scholar 

  • Komakech R, Kang Y, Lee J-H, Omujal F (2017) A review of the potential of phytochemicals from Prunus africana (Hook f.) kalkman stem bark for chemoprevention and chemotherapy of prostate cancer. Evid-Based Compl Altern Med 2017:3014019. https://doi.org/10.1155/2017/3014019

    Article  Google Scholar 

  • Koňariková K, Ježovičová M, Keresteš J, Gbelcová H, Ďuračková Z, Žitňanová IS (2015) Anticancer effect of black tea extract in human cancer cell lines. Springerplus 4:127. https://doi.org/10.1186/s40064-015-0871-4

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kondo M, MacKinnon SL, Craft CC, Matchett MD, Hurta RA, Neto CC (2011) Ursolic acid and its esters: occurrence in cranberries and other Vaccinium fruit and effects on matrix metalloproteinase activity in DU145 prostate tumor cells. J Sci Food Agric 91:789–796

    Article  CAS  PubMed  Google Scholar 

  • Koprowska K, Hartman ML, Sztiller-Sikorska M, Czyz ME (2013) Parthenolide enhances dacarbazine activity against melanoma cells. Anti-Cancer Drugs 24:835–845

    Article  CAS  PubMed  Google Scholar 

  • Kumar G, Mittal S, Sak K, Tuli HS (2016) Molecular mechanisms underlying chemopreventive potential of curcumin: current challenges and future perspectives. Life Sci 148:313–328

    Article  PubMed  CAS  Google Scholar 

  • Lam SS, Ho ES, He BL, Wong WW, Cher CY, Ng NK, Man CH, Gill H, Cheung AM, Ip HW, So CC, Tamburini J, So CW, Ho DN, Au CH, Chan TL, Ma ES, Liang R, Kwong YL, Leung AY (2016) Homoharringtonine (omacetaxine mepesuccinate) as an adjunct for FLT3-ITD acute myeloid leukemia. Sci Transl Med 8:359ra129

    Article  PubMed  CAS  Google Scholar 

  • Lanasa MC, Andritsos L, Brown JR, Gabrilove J, Caligaris-Cappio F, Ghia P, Larson RA, Kipps TJ, Leblond V, Milligan DW, Janssens A, Johnson AJ, Heerema NA, Bühler A, Stilgenbauer S, Devin J, Hallek M, Byrd JC, Grever MR (2015) Final results of EFC6663: a multicenter, international, phase 2 study of alvocidib for patients with fludarabine-refractory chronic lymphocytic leukemia. Leuk Res 39:495–500

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Lee SY, Kim HH, Park SU (2015) Recent studies on betulinic acid and its biological and pharmacological activity. EXCLI J 14:199–203

    PubMed Central  PubMed  Google Scholar 

  • Lewinska A, Adamczyk-Grochala J, Ewa Kwasniewicz E, Deregowska A, Wnuk M (2017) Ursolic acid-mediated changes in glycolytic pathway promote cytotoxic autophagy and apoptosis in phenotypically different breast cancer cells. Apopstosis 22:800–815

    Article  CAS  Google Scholar 

  • Li XJ, Jiang ZZ, Zhang LY (2014) Triptolide: progress on research in pharmacodynamics and toxicology. J Ethnopharmacol 155:67–79

    Article  PubMed  CAS  Google Scholar 

  • Li F, Zhang J, Arfuso F, Chinnathambi A, Zayed ME, Alharbi SA, Kumar AP, Ahn KS, Sethi G (2015) NF-κB in cancer therapy. Arch Toxicol 89:711–731

    Article  CAS  PubMed  Google Scholar 

  • Li X, Mao Y, Li K, Shi T, Yao H, Yao J, Wang S (2016) Pharmacokinetics and tissue distribution study in mice of triptolide-loaded lipid emulsion and accumulation effect on pancreas. Drug Deliv 23:1344–1354

    CAS  PubMed  Google Scholar 

  • Liang X, Grue-Sørensen G, Petersen AK, Högberg T (2012) Semisynthesis of ingenol 3-angelate (PEP005): efficient stereoconservative angeloylation of alcohols. Synlett 23:2647–2652

    Article  CAS  Google Scholar 

  • Liang X, Grue-Sørensen G, Mansson K, Vedsø P, Soor A, Stahlhut M, Bertelsen M, Engell KM, Högberg T (2013) Syntheses, biological evaluation and SAR of ingenol mebutate analogues for treatment of actinic keratosis and non-melanoma skin cancer. Bioorg Med Chem Lett 23:5624–5629

    Article  PubMed  CAS  Google Scholar 

  • Lien JC, Lin MW, Chang SJ, Lai KC, Huang AC, Yu FS, Chung JG (2017) Tetrandrine induces programmed cell death in human oral cancer CAL 27 cells through the reactive oxygen species production and caspase-dependent pathways and associated with beclin-1-induced cell autophagy. Environ Toxicol 32:329–343

    Article  PubMed  CAS  Google Scholar 

  • Lin YT, Huang AC, Kuo CL, Yang JS, Lan YH, Yu CC, Huang WW, Chung JG (2013) Induction of cell cycle arrest and apoptosis in human osteosarcoma U-2 OS cells by Solanum lyratum extracts. Nutr Cancer 65:469–479

    Article  PubMed  Google Scholar 

  • Liu YH, Ou Y (2013) Progress in the research of structure and pharmacological activity of parthenolide. Chin J Pharm Biotechnol 20:586–589

    Google Scholar 

  • Liu J, Wang Z (2015) Increased oxidative stress as a selective anticancer therapy. Oxidative Med Cell Longev 2015:294303. https://doi.org/10.1155/2015/294303

    Article  CAS  Google Scholar 

  • Liu T, Liu X, Li W (2016a) Tetrandrine, a Chinese plant-derived alkaloid, is a potential candidate for cancer chemotherapy. Oncotarget 7:40800–40815

    PubMed Central  PubMed  Google Scholar 

  • Liu W, Zhai Y, Heng X, Che FY, Chen W, Sun D, Zhai G (2016b) Oral bioavailability of curcumin: problems and advancements. J Drug Target 24:694–702

    Article  PubMed  CAS  Google Scholar 

  • Liu WC, Gonga T, Zhu P (2016c) Advances in exploring alternative Taxol sources. RSC Adv 6:48800–48809

    Article  CAS  Google Scholar 

  • Liu R, Ji P, Liu B, Qiao H, Wang X, Zhou L, Deng T, Ba Y (2017) Apigenin enhances the cisplatin cytotoxic effect through p53-modulated apoptosis. Oncol Lett 13:1024–1030

    Article  PubMed  CAS  Google Scholar 

  • Long J, Ding YH, Wang PP, Zhang Q, Chen Y (2013) Protection-group-free semisyntheses of parthenolide and its cyclopropyl analogue. J Org Chem 78:10512–10518

    Article  PubMed  CAS  Google Scholar 

  • Long J, Zhang SF, Wang PP, Zhang XM, Yang ZJ, Zhang Q, Chen Y (2014) Total syntheses of parthenolide and its analogues with macrocyclic stereocontrol. J Med Chem 57:7098–7112

    Article  PubMed  CAS  Google Scholar 

  • Long J, Ding YH, Wang PP, Zhang Q, Chen Y (2016) Total syntheses and structure–activity relationship study of parthenolide analogues. Tetrahedron Lett 57:874–877

    Article  CAS  Google Scholar 

  • Lü S, Wang J (2014) Homoharringtonine and omacetaxine for myeloid hematological malignancies. J Hematol Oncol 7:2. https://doi.org/10.1186/1756-8722-7-2

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Lu Y, Li F, Xu T, Sun J (2017) Tetrandrine prevents multidrug resistance in the osteosarcoma cell line, U-2OS, by preventing pgp overexpression through the inhibition of NF-κB signaling. Int J Mol Med 39:993–1000

    Article  CAS  PubMed  Google Scholar 

  • Luo R, Fang D, Chu P, Wu H, Zhang Z, Tang Z (2016) Multiple molecular targets in breast cancer therapy by betulinic acid. Biomed Pharmacother 84:1321–1330

    Article  CAS  PubMed  Google Scholar 

  • Ma D, Lu B, Feng C, Wang C, Wang Y, Luo T, Feng J, Jia H, Chi G, Luo Y, Ge P (2016) Deoxypodophyllotoxin triggers parthanatos in glioma cells via induction of excessive ROS. Cancer Lett 371:194–204

    Article  PubMed  CAS  Google Scholar 

  • Ma JW, Zhang Y, Ye JC, Li R, Wen YL, Huang JX, Zhong XY (2017) Tetrandrine exerts a radiosensitization effect on human glioma through inhibiting proliferation by attenuating ERK phosphorylation. Biomol Ther 25:186–193

    Article  Google Scholar 

  • Mahoney S, Arfuso F, Millward M, Dharmarajan A (2014) The effects of phenoxodiol on the cell cycle of prostate cancer cell lines. Cancer Cell Int 14:110. https://doi.org/10.1186/s12935-014-0110-z

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Maiyo F, Moodley R, Singha M (2016) Phytochemistry, cytotoxicity and apoptosis studies of β-sitosterol-3-O-glucoside and β-amyrin from Prunus africana. Afr J Tradit Compl Altern Med 13:105–112

    Article  CAS  Google Scholar 

  • Mao JT, Xue B, Smoake J, Lu QY, Park H, Henning SM, Burns W, Bernabei A, Elashoff D, Serio KJ, Massie L (2016) MicroRNA-19a/b mediates grape seed procyanidin extract-induced anti-neoplastic effects against lung cancer. J Nutr Biochem 34:118–125

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Matias D, Bessa C, Simões MF, Reis CP, Saraiva L, Rijo P (2017) Natural products as lead protein kinase c modulators for cancer therapy Atta-ur-Rahman FRS Studies in natural products chemistry, bioactive natural products. Elsevier, Amsterdam, 45–79

    Google Scholar 

  • Meng C, Zhu H, Song H, Wang Z, Huang G, Li D, Ma Z, Ma J, Qin Q, Sun X, Ma J (2014) Targets and molecular mechanisms of triptolide in cancer therapy. Chin J Cancer Res 26:622–626

    PubMed Central  PubMed  Google Scholar 

  • Meng Z, Lv Q, Lu J, Yao H, Lv X, Jiang F, Lu A, Zhang G (2016) Prodrug strategies for paclitaxel. Int J Mol Sci 17:E796. https://doi.org/10.3390/ijms17050796

    Article  PubMed  CAS  Google Scholar 

  • Millsop JW, Sivamani RK, Fazel N (2013) Botanical agents for the treatment of nonmelanoma skin cancer. Dermatol Res Pract 2013:837152. https://doi.org/10.1155/2013/837152

    Article  Google Scholar 

  • Mishra BB, Tiwari VK (2011) Natural products: an evolving role in future drug discovery. Eur J Med Chem 46:4769–4807

    Article  CAS  PubMed  Google Scholar 

  • Mock CD, Jordan BC, Selvam C (2015) Recent advances of curcumin and its analogues in breast cancer prevention and treatment. RSC Adv 5:75575–75588

    Article  PubMed  CAS  Google Scholar 

  • Modi S, Kir D, Giri B, Majumder K, Arora N, Dudeja V, Banerjee S, Saluja AK (2016) Minnelide overcomes oxaliplatin resistance by downregulating DNA repair pathway in pancreatic cancer. J Gastrointest Surg 20:13–24

    Article  PubMed  Google Scholar 

  • Mohandas KM, Desai DC (1999) Epidemiology of digestive tract cancers in India. V. Large and small bowel. Indian J Gastroenterol 18:118–121

    PubMed  CAS  Google Scholar 

  • Moore A, Pinkerton R (2009) Vincristine: can its therapeutic index be enhanced? Pediatr Blood Cancer 53:1180–1187

    Article  PubMed  Google Scholar 

  • Mora E, Smith EML, Donohoe C, Hertz D (2016) Vincristine-induced peripheral neuropathy in pediatric cancer patients. Am J Cancer Res 6:2416–2430

    PubMed Central  PubMed  CAS  Google Scholar 

  • Moselhy J, Srinivasan S, Ankem MK, Damodaran C (2015) Natural products that target cancer stem cells. Anticancer Res 35:5773–5788

    PubMed  PubMed Central  CAS  Google Scholar 

  • Mujumdar N, Mackenzie TN, Dudeja V, Chugh R, Antonoff MB, Borja-Cacho D, Sangwan V, Dawra R, Vickers SM, Saluja AK (2010) Triptolide induces cell death in pancreatic cancer cells by apoptotic and autophagic pathways. Gastroenterology 139:598–608

    Article  PubMed  CAS  Google Scholar 

  • Mujumdar N, Banerjee S, Chen Z, Sangwan V, Chugh R, Dudeja V, Yamamoto M, Vickers SM, Saluja AK (2014) Triptolide activates unfolded protein response leading to chronic ER stress in pancreatic cancer cells. Am J Physiol Gastrointest Liver Physiol 306:1011–1020

    Article  CAS  Google Scholar 

  • Muthaura CN, Keriko JM, Mutai C, Yenesew A, Gathirwa JW, Irungu BN, Nyangacha R, Mungai GM, Derese S (2015) Antiplasmodial potential of traditional phytotherapy of some remedies used in treatment of malaria in Meru-Tharaka Nithi County of Kenya. J Ethnopharmacol 175:315–323

    Article  CAS  PubMed  Google Scholar 

  • Muto N, Tomokuni T, Haramoto M, Tatemoto H, Nakanishi T, Inatomi Y, Murata H, Inada A (2008) Isolation of apoptosis- and differentiation-inducing substances toward human promyelocytic leukemia HL-60 cells from leaves of Juniperus taxifolia. Biosci Biotechnol Biochem 72:477–484

    Article  CAS  PubMed  Google Scholar 

  • Nakshatri H, Appaiah HN, Anjanappa M, Gilley D, Tanaka H, Badve S, Crooks PA, Mathews W, Sweeney C, Bhat-Nakshatri P (2015) NF-κB-dependent and independent epigenetic modulation using the novel anticancer agent DMAPT. Cell Death Dis 6:e1608. https://doi.org/10.1038/cddis.2014.569

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Nazha A, Kantarjian H, Cortes J, Quintás-Cardama A (2013) Omacetaxine mepesuccinate (synribo)-newly launched in chronic myeloid leukemia. Exp Opin Pharmacother 14:1977–1986

    Article  CAS  Google Scholar 

  • Nie XP, Yao F, Yue XD, Li GS, Dai SJ (2014) New eudesmane-type sesquiterpenoid from Solanum lyratum with cytotoxic activity. Nat Prod Res 28:641–645

    Article  CAS  PubMed  Google Scholar 

  • Niedzwiecki A, Roomi MW, Kalinovsky T, Rath M (2016) Anticancer efficacy of polyphenols and their combinations. Forum Nutr 8:E552. https://doi.org/10.3390/nu8090552

    Article  CAS  Google Scholar 

  • Njoya EM, Munvera AM, Mkounga P, Nkengfack AE, McGaw LJ (2017) Phytochemical analysis with free radical scavenging, nitric oxide inhibition and antiproliferative activity of Sarcocephalus pobeguinii extracts. BMC Compl Altern Med 17:199. https://doi.org/10.1186/s12906-017-1712-5

    Article  Google Scholar 

  • Nomura A, McGinn O, Dudeja V, Sangwan V, Saluja AK, Banerjee S (2015) Minnelide effectively eliminates CD133+ side population in pancreatic cancer. Mol Cancer 14:200. https://doi.org/10.1186/s12943-015-0470-6

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Nwodo JN, Ibezim A, Simoben CV, Ntie-Kang F (2016) Exploring cancer therapeutics with natural products from african medicinal plants, Part II: Alkaloids, terpenoids and flavonoids. Anti Cancer Agents Med Chem 16:108–127

    Article  CAS  Google Scholar 

  • Ochwangi DO, Kimwele CN, Oduma JA, Gathumbi PK, Mbaria JM, Kiama SG (2014) Medicinal plants used in treatment and management of cancer in Kakamega County, Kenya. J Ethnopharmacol 151:1040–1055

    Article  Google Scholar 

  • Ogbourne SM, Suhrbier A, Jones B, Cozzi SJ, Boyle GM, Morris M, McAlpine D, Johns J, Scott TM, Sutherland KP, Gardner JM, Le TT, Lenarczyk A, Aylward JH, Parsons PG (2004) Antitumor activity of 3-ingenyl angelate: plasma membrane and mitochondrial disruption and necrotic cell death. Cancer Res 64:2833–2839

    Article  CAS  PubMed  Google Scholar 

  • Oing C, Seidel C, von Amsberg G, Oechsle K, Bokemeyer C (2016) Pharmacotherapeutic treatment of germ cell tumors: standard of care and recent developments. Exp Opin Pharmacother 17:545–560

    Article  CAS  Google Scholar 

  • Omosa LK, Midiwo JO, Masila VM, Gisacho BM, Munayi R, Francisca-Kamakama, Chemutai KP, Elhaboob G, Saeed ME, Hamdoun S, Kuete V, Efferth T (2016) Cytotoxicity of 91 Kenyan indigenous medicinal plants towards human CCRF-CEM leukemia cells. J Ethnopharmacol 179:177–196

    Article  CAS  PubMed  Google Scholar 

  • Orhan IE, Tosun F, Gülpınar AR, Kartal M, Duran A, Mihoglugil F, Akalgan D (2015) LC-MS quantification of parthenolide and cholinesterase inhibitory potential of selected Tanacetum L. (Emend. Briq.) taxa. Phytochem Lett 11:347–352

    Article  CAS  Google Scholar 

  • Orofino MR, Grootjans S, Biavatti MW, Vandenabeele P, D’Herde K (2012) Sesquiterpene lactones as drugs with multiple targets in cancer treatment: focus on parthenolide. Anti-Cancer Drugs 23:883–896

    Google Scholar 

  • Ortensi B, Setti M, Osti D, Pelicci G (2013) Cancer stem cell contribution to glioblastoma invasiveness. Stem Cell Res Ther 4:18. https://doi.org/10.1186/scrt166

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Osterman CJD, Wall NR (2015) Curcumin and pancreatic cancer: a research and clinical update. J Nat Sci 1:e124

    Google Scholar 

  • Ostrom QT, Gittleman H, Stetson L, Virk SM, Barnholtz-Sloan JS (2015) Epidemiology of gliomas. Cancer Treat Res 163:1–14

    Article  PubMed  Google Scholar 

  • Pareek A, Suthar M, Rathore GS, Bansal V (2011) Feverfew Tanacetum parthenium L.: a systematic review. Pharmacogn Rev 5:103–110

    Article  PubMed Central  PubMed  Google Scholar 

  • Patel JJ, Acharya SR, Acharya NS (2014) Clerodendrum serratum (L.) Moon. – a review on traditional uses, phytochemistry and pharmacological activities. J Ethnopharmacol 154:268–285

    Article  CAS  PubMed  Google Scholar 

  • Pattnaik B, Lakshmi JK, Kavitha R, Jagadeesh B, Bhattacharjee D, Jain N, Mallavadhani UV (2017) Synthesis, structural studies, and cytotoxic evaluation of novel ursolic acid hybrids with capabilities to arrest breast cancer cells in mitosis. J Asian Nat Prod Res 19:260–271

    Article  CAS  PubMed  Google Scholar 

  • Pavan AR, Silva GD, Jornada DH, Chiba DE, Fernandes GF, Man Chin C, Dos Santos JL (2016) Unraveling the anticancer effect of curcumin and resveratrol. Forum Nutr 8:E628. https://doi.org/10.3390/nu8110628

    Article  CAS  Google Scholar 

  • Pawar VK, Panchal SB, Singh Y, Meher JG, Sharma K, Singh P, Bora HK, Singh A, Datta D, Chourasia MK (2014) Immunotherapeutic vitamin e nanoemulsion synergies the antiproliferative activity of paclitaxel in breast cancer cells via modulating Th1 and Th2 immune response. J Control Release 196:295–306

    Article  CAS  PubMed  Google Scholar 

  • Peese K (2010) New agents for the treatment of leukemia: discovery of DMAPT (LC-1). Drug Discov Today 15:322. https://doi.org/10.1016/j.drudis.2009.08.008

    Article  Google Scholar 

  • Peng W, Qin R, Li X, Zhou H (2013) Botany, phytochemistry, pharmacology, and potential application of Polygonum cuspidatum Sieb.et Zucc.: a review. J Ethnopharmacol 148:729–745

    Article  CAS  PubMed  Google Scholar 

  • Perrone D, Ardito F, Giannatempo G, Dioguardi M, Troiano G, Lo Russo L, De Lillo A, Laino L, Lo Muzio L (2015) Biological and therapeutic activities and anticancer properties of curcumin. Exp Ther Med 10:1615–1623

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Pichette A, Liu H, Roy C, Tanguay S, Simard F, Lavoie S (2004) Selective oxidation of botulin for the preparation of betulinic acid, an antitumoral compound. Synth Commun 34:3925–3937

    Article  CAS  Google Scholar 

  • Pimentel-Gutiérrez HJ, Bobadilla-Morales L, Barba-Barba CC, Ortega-De-La-Torre C, Sánchez-Zubieta FA, Corona-Rivera JR, González-Quezada BA, Armendáriz-Borunda JS, Silva-Cruz R, Corona-Rivera A (2016) Curcumin potentiates the effect of chemotherapy against acute lymphoblastic leukemia cells via downregulation of NF-κB. Oncol Lett 12:4117–4124

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Pisha E, Chai H, Lee IS, Chagwedera TE, Farnsworth NR, Cordell GA, Beecher CW, Fong HH, Kinghorn AD, Brown DH (1995) Discovery of betulinic acid a selective inhibitor of human-melanoma that functions by induction of apoptosis. Nat Med 10:1046–1051

    Article  Google Scholar 

  • Potze L, Di Franco S, Grandela C, Pras-Raves ML, Picavet DI, van Veen HA, van Lenthe H, Mullauer FB, van der Wel NN, Luyf A, van Kampen AH, Kemp S, Everts V, Kessler JH, Vaz FM, Medema JP (2016a) Betulinic acid induces a novel cell death pathway that depends on cardiolipin modification. Oncogene 35:427–437

    Article  CAS  PubMed  Google Scholar 

  • Potze L, Di Franco S, Kessler JH, Stassi G, Medema JP (2016b) Betulinic acid kills colon cancer stem cells. Curr Stem Cell Res Ther 11:427–433

    Article  CAS  PubMed  Google Scholar 

  • Puneeth HR, Ananda H, Kumar KSS, Rangappa KS, Sharada AC (2016) Synthesis and antiproliferative studies of curcumin pyrazole derivatives. Med Chem Res 25:1842–1851

    Article  CAS  Google Scholar 

  • Qiu W, Zhang AL, Tian Y (2017) Tetrandrine triggers an alternative autophagy in DU145 cells. Oncol Lett 13:3734–3738

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Rahimi HR, Nedaeinia R, Shamloo AS, Nikdoust S, Oskuee RK (2016) Novel delivery system for natural products: nano-curcumin formulations. Avicenna J Phytomed 6:383–398

    PubMed Central  PubMed  Google Scholar 

  • Ramasamy TS, Ayob AZ, Myint HHL, Thiagarajah S, Amini F (2015) Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights into the mechanism of the therapeutic efficacy. Cancer Cell Int 15:96. https://doi.org/10.1186/s12935-015-0241-x

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ramsay JR, Suhrbier A, Aylward JH, Ogbourne S, Cozzi SJ, Poulsen MG, Baumann KC, Welburn P, Redlich GL, Parsons PG (2011) The sap from Euphorbia peplus is effective against human nonmelanoma skin cancers. Br J Dermatol 164:633–636

    CAS  PubMed  Google Scholar 

  • Redondo-Blanco S, Fernández J, Gutiérrez-del-Río I, Villar CJ, Lombó F (2017) New insights toward colorectal cancer chemotherapy using natural bioactive compounds. Front Pharmacol 8:109. https://doi.org/10.3389/fphar.2017.00109

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Réthy B, Csupor-Löffler B, Zupkó I, Hajdú Z, Máthé I, Hohmann J, Rédei T, Falkay G (2007) Antiproliferative activity of Hungarian Asteraceae species against human cancer cell lines. Part I. Phytother Res 21:1200–1208

    Article  PubMed  Google Scholar 

  • Rivard C, Geller M, Schnettler E, Saluja M, Vogel RI, Saluja A, Ramakrishnan S (2014) Inhibition of epithelial ovarian cancer by Minnelide, a water-soluble pro-drug. Gynecol Oncol 135:318–324

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Rizk AM, Hammouda FM, El-Missiry MM, Radwan HM, Evans FJ (1985) Biologically active diterpene esters from Euphorbia peplus. Phytochemistry 24:1605–1606

    Article  CAS  Google Scholar 

  • Rosen RH, Gupta AK, Tyring SK (2012) Dual mechanism of action of ingenol mebutate gel for topical treatment of actinic keratoses: rapid lesion necrosis followed by lesion-specific immune response. J Am Acad Dermatol 66:486–493

    Article  CAS  PubMed  Google Scholar 

  • Roshan SK, Spano AD, McKinney AM, Nascene DR (2017) Potentially reversible acute cerebellar toxicity associated with minnelide. Neuroradiology 59:419–421

    Article  Google Scholar 

  • Rosshandler Y, Shen AQ, Cortes J, Khoury HJ (2016) Omacetaxine mepesuccinate for chronic myeloid leukemia. Expert Rev Hematol 9:419–424

    Article  CAS  PubMed  Google Scholar 

  • Rousalova I, Banerjee S, Sangwan V, Evenson K, McCauley JA, Kratzke R, Vickers SM, Saluja A, D’Cunha J (2013) Minnelide: a novel therapeutic that promotes apoptosis in non-small cell lung carcinoma in vivo. PLoS One 8:e77411. https://doi.org/10.1371/journal.pone.0077411

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Sales JM, Resurreccion AVA (2014) Resveratrol in peanuts. Crit Rev Food Sci Nutr 54:734–770

    Article  CAS  PubMed  Google Scholar 

  • Sarek J, Kvasnica M, Vlk M, Urban M, Dzubak P, Hajduch M (2011) The potential of triterpenoids in the treatment of melanoma. In: Murph M (ed) Research on melanoma-a glimpse into current directions and future trends. InTech, Rijeka, pp 125–158

    Google Scholar 

  • Schwertheim S, Wein F, Lennartz K, Worm K, Schmid KW, Sheu-Grabellus SY (2017) Curcumin induces G2/M arrest, apoptosis, NF-κB inhibition, and expression of differentiation genes in thyroid carcinoma cells. J Cancer Res Clin Oncol 143:1143–1154

    Article  CAS  PubMed  Google Scholar 

  • Seca AML, Pinto DCGA, Silva AMS (2015) The current status of bioactive metabolites from the genus Juniperus. In: Gupta VK (ed) Bioactive phytochemicals: perspectives for modern medicine, vol 3. Daya Publishing House, New Delhi, pp 367–410

    Google Scholar 

  • Seca AML, Silva AMS, Pinto DCGA (2017) Parthenolide and parthenolide-like sesquiterpene lactones as multiple targets drugs: current knowledge and new developments. In: Atta-Ur-Rahman FRS (ed) Studies in natural products chemistry (bioactive natural products). Elsevier, Amsterdam, pp 337–372

    Google Scholar 

  • Sen S, Hassane DC, Corbett C, Becker MW, Jordan CT, Guzman ML (2013) Novel mTOR inhibitory activity of ciclopirox enhances parthenolide antileukemia activity. Exp Hematol 41:799–807

    Article  CAS  PubMed  Google Scholar 

  • Seo HS, Jo JK, Ku JM, Choi HS, Choi YK, Woo JK, Kim HI, Kang SY, Lee KM, Nam KW, Park N, Jang BH, Shin YC, Ko SG (2015) Induction of caspase dependent extrinsic apoptosis through inhibition of signal transducer and activator of transcription 3 (STAT3) signalling in HER2-overexpressing BT-474breast cancer cells. Biosci Rep 35:e00276. https://doi.org/10.1042/BSR20150165

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Serova M, Ghoul A, Benhadji KA, Faivre S, Le Tourneau C, Cvitkovic E, Lokiec F, Lord J, Ogbourne SM, Calvo F, Raymond E (2008) Effects of protein kinase C modulation by PEP005, a novel ingenol angelate, on mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling in cancer cells. Mol Cancer Ther 7:915–922

    Article  CAS  PubMed  Google Scholar 

  • Shah NN, Cole DE, Lester-McCully CM, Wayne AS, Warren KE, Widemann BC (2016a) Plasma and cerebrospinal fluid pharmacokinetics of vincristine and vincristine sulfate liposomes injection (VSLI, marqibo®) after intravenous administration in non-human primates. Investig New Drugs 34:61–65

    Article  CAS  Google Scholar 

  • Shah NN, Merchant MS, Cole DE, Jayaprakash N, Bernstein D, Delbrook C, Richards K, Widemann BC, Wayne AS (2016b) Vincristine sulfate liposomes injection (VSLI, Marqibo®): results from a phase I study in children, adolescents, and young adults with refractory solid tumors or leukemias. Pediatr Blood Cancer 63:997–1005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shankar E, Zhang A, Franco D, Gupta S (2017) Betulinic acid-mediated apoptosis in human prostate cancer cells involves p53 and nuclear factor-kappa b (NF-κB) pathways. Molecules 22:E264. https://doi.org/10.3390/molecules22020264

    Article  PubMed  CAS  Google Scholar 

  • Shanmugam MK, Dai X, Kumar AP, Tan BK, Sethi G, Bishayee A (2013) Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies. Biochem Pharmacol 85:1579–1587

    Article  CAS  PubMed  Google Scholar 

  • Shanmugam MK, Rane G, Kanchi MM, Arfuso F, Chinnathambi A, Zayed ME, Alharbi SA, Tan BK, Kumar AP, Sethi G (2015) The multifaceted role of curcumin in cancer prevention and treatment. Molecules 20:2728–2769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen AQ, Munteanu M, Khoury HJ (2014) Updated product label allows home administration of omacetaxine mepesuccinate. Oncologist 19:e14. https://doi.org/10.1634/theoncologist.2014-0230

    Article  PubMed Central  PubMed  Google Scholar 

  • Singh S, Sharma B, Kanwar SS, Kumar A (2016) Lead phytochemicals for anticancer drug development. Front Plant Sci 7:1667. https://doi.org/10.3389/fpls.2016.01667

    Article  PubMed Central  PubMed  Google Scholar 

  • Sinha R, Anderson DE, McDonald SS, Greenwald P (2003) Cancer risk and diet in India. J Postgrad Med 49:222–228

    PubMed  CAS  Google Scholar 

  • Sinha D, Sarkar N, Biswas J, Bishayee A (2016) Resveratrol for breast cancer prevention and therapy: preclinical evidence and molecular mechanisms. Semin Cancer Biol 40–41:209–232

    Article  PubMed  CAS  Google Scholar 

  • Sivakumar P, Mengani S, Vijayabaskaran M, Kumar RS, Perumal P, Jayakar B (2010) Antitumor and antioxidant activities of Triumfetta rhomboidea against Ehrlich ascites carcinoma bearing Swiss Albino mice. Res J Pharm Biol Chem Sci 1:486–494

    Google Scholar 

  • Soladoye MO, Amusa NA, Raji-Esan SO, Chukwuma EC, Taiwo AA (2010) Ethnobotanical survey of anticancer plants in Ogun State, Nigeria. Ann Biol Res 1:261–273

    Google Scholar 

  • Soliman HH (2017) nab-paclitaxel as a potential partner with checkpoint inhibitors in solid tumors. Onco Target Ther 10:101–112

    Article  CAS  Google Scholar 

  • Soliman MM, Abdo Nassan M, Ismail TA (2014) Immunohistochemical and molecular study on the protective effect of curcumin against hepatic toxicity induced by paracetamol in Wistar rats. BMC Complement Altern Med 14:457. https://doi.org/10.1186/1472-6882-14-457

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Song JM, Qian X, Upadhyayya P, Hong KH, Kassie F (2014) Dimethylaminoparthenolide, a water soluble parthenolide, suppresses lung tumorigenesis through down-regulating the STAT3 signaling pathway. Curr Cancer Drug Tar 14:59–69

    Article  CAS  Google Scholar 

  • Song XL, Liu S, Jiang Y, Gu LY, Xiao Y, Wang X, Cheng L, Li XT (2017a) Targeting vincristine plus tetrandrine liposomes modified with DSPE-PEG2000-transferrin in treatment of brain glioma. Eur J Pharm Sci 96:129–140

    Article  CAS  PubMed  Google Scholar 

  • Song JM, Molla K, Anandharaj A, Cornax I, O’Sullivan MG, Kirtane AR, Panyam J, Kassie F (2017b) Triptolide suppresses the in vitro and in vivo growth of lung cancer cells by targeting hyaluronan-CD44/RHAMM signalling. Oncotarget 8:26927–26940

    Google Scholar 

  • Sordillo PP, Helson L (2015) Curcumin and cancer stem cells: curcumin has asymmetrical effects on cancer and normal stem cells. Anticancer Res 35:599–614

    CAS  PubMed  Google Scholar 

  • Sri Ramya PV, Angapelly S, Guntuku L, Singh Digwal C, Nagendra Babu B, Naidu VG, Kamal A (2017) Synthesis and biological evaluation of curcumin inspired indole analogues as tubulin polymerization inhibitors. Eur J Med Chem 127:100–114

    Article  CAS  PubMed  Google Scholar 

  • Strimpakos AS, Sharma RA (2008) Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal 10:511–546

    Article  CAS  PubMed  Google Scholar 

  • Sung B, Chung HY, Kim ND (2016) Role of apigenin in cancer prevention via the induction of apoptosis and autophagy. J Cancer Prev 21:216–226

    Article  PubMed Central  PubMed  Google Scholar 

  • Tang D, Chen K, Huang L, Li J (2017) Pharmacokinetic properties and drug interactions of apigenin, a natural flavone. Exp Opin Drug Metab Toxicol 13:323–330

    Article  CAS  Google Scholar 

  • Tariq A, Sadia S, Pan K, Ullah I, Mussarat S, Sun F, Abiodun OO, Batbaatar A, Li Z, Song D, Xiong Q, Ullah R, Khan S, Basnet BB, Kumar B, Islam R, Adnan M (2017) A systematic review on ethnomedicines of anticancer plants. Phytother Res 31:202–264

    Article  PubMed  Google Scholar 

  • Teoh PL, Cheng AYF, Liau M, Lem FF, Kaling GP, Chua FN, Cheong BE (2017) Chemical composition and cytotoxic properties of Clinacanthus nutans root extracts. Pharm Biol 55:394–401

    Article  CAS  PubMed  Google Scholar 

  • Torquato HFV, Goettert MI, Justo GZ, Paredes-Gamero EJ (2017) Anticancer phytometabolites targeting cancer stem cells. Curr Genomics 18:156–174

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Tsai HY, Ho CT, Chen YK (2017) Biological actions and molecular effects of resveratrol, pterostilbene, and 3′-hydroxypterostilbene. J Food Drug Anal 25:134–147

    Article  CAS  PubMed  Google Scholar 

  • Turek M, Krzyczmonik M, Balczewski P (2016) New hopes in cancer battle-a review of new molecules and treatment strategies. Med Chem 12:700–719

    Article  PubMed  CAS  Google Scholar 

  • Tzogani K, Nagercoil N, Hemmings RJ, Samir B, Gardette J, Demolis P, Salmonson T, Pignatti F (2014) The European medicines agency approval of ingenol mebutate (Picato) for the cutaneous treatment of non-hyperkeratotic, non-hypertrophic actinic keratosis in adults: summary of the scientific assessment of the committee for medicinal products for human use (CHMP). Eur J Dermatol 24:457–463

    PubMed  CAS  Google Scholar 

  • Uwagawa T, Yanaga K (2015) Effect of NF-κB inhibition on chemoresistance in biliary-pancreatic cancer. Surg Today 45:1481–1488

    Article  PubMed  CAS  Google Scholar 

  • Varoni EM, Lo Faro AF, Sharifi-Rad J, Iriti M (2016) Anticancer molecular mechanisms of resveratrol. Front Nutr 3:8. https://doi.org/10.3389/fnut.2016.00008

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Vazquez-Santillan K, Melendez-Zajgla J, Jimenez-Hernandez L, Martínez-Ruiz G, Maldonado V (2015) NF-κB signaling in cancer stem cells: a promising therapeutic target. Cell Oncol 38:327–339

    Article  CAS  Google Scholar 

  • Velde ME, Kaspers GL, Abbink FCH, Wilhelm AJ, Ket JCF, Berg MH (2017) Vincristine-induced peripheral neuropathy in children with cancer: a systematic review. Crit Rev Oncol Hematol 114:114–130

    Article  PubMed  Google Scholar 

  • Vergote I, Leamon CP (2015) Vintafolide: a novel targeted therapy for the treatment of folate receptor expressing tumors. Ther Adv Med Oncol 7:206–218

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Vipasha S, Hardeep K, Tarun K, Tullika M (2016) Traditional Indian herb Catharanthus roseus used as cancer treatment: a review. Int J Pharmacogn Phytochem Res 8:1926–1928

    Google Scholar 

  • Viral D, Shivanand P, Jivani NP (2011) Anticancer evaluation of Adiantum venustum Don. J Young Pharma 3:48–54

    Article  CAS  Google Scholar 

  • Waechter F, Silva GS, Willig J, de Oliveira CB, Vieira BD, Trivella DB, Zimmer AR, Buffon A, Pilger DA, Gnoatto S (2017) Design, synthesis, and biological evaluation of betulinic acid derivatives as new antitumor agents for leukemia. Anticancer Agents Med Chem (Online). https://doi.org/10.2174/1871521409666170412143638

  • Wang YJ, Pan MH, Cheng AL, Lin LI, Ho YS, Hsieh CY, Lin JK (1997) Stability of curcumin in buffer solutions and characterization of its degradation products. J Pharm Biomed Anal 15:1867–1876

    Article  CAS  PubMed  Google Scholar 

  • Wang YR, Xu Y, Jiang ZZ, Guerram M, Wang B, Zhu X, Zhang LY (2015a) Deoxypodophyllotoxin induces G2/M cell cycle arrest and apoptosis in SGC-7901 cells and inhibits tumor growth in vivo. Molecules 20:1661–1675

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang Y, Wang B, Guerram M, Sun L, Shi W, Tian C, Zhu X, Jiang Z, Zhang L (2015b) Deoxypodophyllotoxin suppresses tumor vasculature in HUVECs by promoting cytoskeleton remodeling through LKB1-AMPK dependent Rho A activation. Oncotarget 6:29497–29512

    PubMed Central  PubMed  Google Scholar 

  • Wang S, Wang W, Lv H, Zhou J, Shen L, Yin L, Ding Y (2016a) Preparation and evaluation of long-circulating deoxypodophyllotoxin-loaded liposomes using poly(ethylene glycol)-distearoylphosphatidylethanolamine. J Pharm Innov 11:134–142

    Article  Google Scholar 

  • Wang H, Ma D, Wang C, Zhao S, Liu C (2016b) Triptolide inhibits invasion and tumorigenesis of hepatocellular carcinoma MHCC-97H cells through NF-κB signaling. Med Sci Monit 22:1827–1836

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Wang X, Song Y, Su Y, Tian Q, Li B, Quan J, Deng Y (2016c) Are PEGylated liposomes better than conventional liposomes. A special case for vincristine. Drug Deliv 23:1092–1100

    PubMed  CAS  Google Scholar 

  • Wang M, Zhao T, Liu Y, Wang Q, Xing S, Li L, Wang L, Liu L, Gao D (2017a) Ursolic acid liposomes with chitosan modification: promising antitumor drug delivery and efficacy. Mater Sci Eng C 71:1231–1240

    Article  CAS  Google Scholar 

  • Wang S, Wang H, Li T, Li C, Zhou Y, Zhong X (2017b) The selection and stability analysis of stable and high Taxol-producing cell lines from Taxus cuspidate. J For Res. https://doi.org/10.1007/s11676-017-0406-7

  • Watkins R, Wu L, Zhang C, Davis RM, Xu B (2015) Natural product-based nanomedicine: recent advances and issues. Int J Nanomedicine 10:6055–6074

    PubMed Central  PubMed  CAS  Google Scholar 

  • Wen G, Qu XX, Wang D, Chen XX, Tian XC, Gao F, Zhou XL (2016) Recent advances in design, synthesis and bioactivity of paclitaxel-mimics. Fitoterapia 110:26–37

    Article  PubMed  CAS  Google Scholar 

  • WHO (2017) Who factsheets. http://www.who.int/mediacentre/factsheets/fs297/en/. Assessed on 18 Oct 2017

  • Wozniak M, Szulawska-Mroczek A, Hartman ML, Nejc D, Czyz M (2013) Parthenolide complements the cell death-inducing activity of doxorubicin in melanoma cells. Anticancer Res 33:3205–3212

    PubMed  Google Scholar 

  • Woźniak Ł, Skąpska S, Marszałek K (2015) Ursolic acid-A pentacyclic triterpenoid with a wide spectrum of pharmacological activities. Molecules 20:20614–20641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu M, Jiang Z, Duan H, Sun L, Zhang S, Chen M, Wang Y, Gao Q, Song Y, Zhu X, Zhang L (2013) Deoxypodophyllotoxin triggers necroptosis in human non-small cell lung cancer NCI-H460 cells. Biomed Pharmacother 67:701–706

    Article  CAS  PubMed  Google Scholar 

  • Wyrebska A, Gach K, Janecka A (2014) Combined effect of parthenolide and various anticancer drugs or anticancer candidate substances on malignant cells in vitro and in vivo. Mini Rev Med Chem 14:222–228

    Article  PubMed  CAS  Google Scholar 

  • Xi C, Peng S, Wu Z, Zhou Q, Zhou J (2017) Toxicity of triptolide and the molecular mechanisms involved. Biomed Pharmacother 90:531–541

    Article  CAS  PubMed  Google Scholar 

  • Xiao Z, Morris-Natschke SL, Lee KH (2016) Strategies for the optimization of natural leads to anticancer drugs or drug candidates. Med Res Rev 36:32–91

    Article  PubMed  CAS  Google Scholar 

  • Xie CQ, Zhou P, Zuo J, Li X, Chen Y, Chen JW (2016) Triptolide exerts pro-apoptotic and cell cycle arrest activity on drug-resistant human lung cancer A549/Taxol cells via modulation of MAPK and PI3K/Akt signaling pathways. Oncol Lett 12:3586–3590

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Xin Y, Yin F, Qi S, Shen L, Xu Y, Luo L, Lan L, Yin Z (2013) Parthenolide reverses doxorubicin resistance in human lung carcinoma A549 cells by attenuating NF-B activation and HSP70 up-regulation. Toxicol Lett 221:73–82

    Article  PubMed  CAS  Google Scholar 

  • Xu H, Hou Z, Zhang H, Kong H, Li X, Wang H, Xie W (2014) An efficient Trojan delivery of tetrandrine by poly(Nvinylpyrrolidone)-block-poly(epsilon-caprolactone) (PVPb-PCL) nanoparticles shows enhanced apoptotic induction of lung cancer cells and inhibition of its migration and invasion. Int J Nanomedicine 9:231–242

    PubMed  Google Scholar 

  • Xu Y, Li J, Li QJ, Feng YL, Pan F (2017) Betulinic acid promotes TRAIL function on liver cancer progression inhibition through p53/Caspase-3 signaling activation. Biomed Pharmacother 88:349–358

    Article  PubMed  CAS  Google Scholar 

  • Yallapu MM, Nagesh PKB, Jaggi M, Chauhan SC (2015) Therapeutic applications of curcumin nanoformulations. AAPS J 1:1341–1356

    Article  CAS  Google Scholar 

  • Yang J, Liang Q, Wang M, Jeffries C, Smithson D, Tu Y, Boulos N, Jacob MR, Shelat AA, Wu Y, Ravu RR, Gilbertson R, Avery MA, Khan IA, Walker LA, Guy RK, Li XC (2014a) UPLC-MS-ELSD-PDA as a powerful dereplication tool to facilitate compound identification from small-molecule natural product libraries. J Nat Prod 77:902–909

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Yang Y, Chen Y, Zhong ZY, Zhang J, Li F, Jia LL, Liu L, Zhu X, Liu XD (2014b) Validated LC–MS/MS assay for quantitative determination of deoxypodophyllotoxin in rat plasma and its application in pharmacokinetic study. J Pharm Biomed Anal 88:410–415

    Article  PubMed  CAS  Google Scholar 

  • Yang ZJ, Ge WZ, Li QY, Lu Y, Gong JM, Kuang BJ, Xi X, Wu H, Zhang Q, Chen Y (2015) Syntheses and biological evaluation of costunolide, parthenolide, and their fluorinated analogues. J Med Chem 58:7007–7020

    Article  PubMed  CAS  Google Scholar 

  • Yang CY, Lin CK, Lin GJ, Hsieh CC, Huang SH, Ma KH, Shieh YS, Sytwu HK, Chen YW (2017a) Triptolide represses oral cancer cell proliferation, invasion, migration, and angiogenesis in co-inoculation with U937 cells. Clin Oral Investig 21:419–427

    Article  PubMed  Google Scholar 

  • Yang C, Ma X, Wang Z, Zeng X, Hu Z, Ye Z, Shen G (2017b) Curcumin induces apoptosis and protective autophagy in castration-resistant prostate cancer cells through iron chelation. Drug Des Devel Ther 11:431–439

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Yao H, Liu J, Xu S, Zhu Z, Xu J (2017) The structural modification of natural products for novel drug discovery. Exp Opin Drug Discov 12:121–140

    Article  CAS  Google Scholar 

  • Ye LY, Hu S, Xu HE, Xu RR, Kong H, Zeng XN, Xie WP, Wang H (2017) The effect of tetrandrine combined with cisplatin on proliferation and apoptosis of A549/DDP cells and A549 cells. Cancer Cell Int 17:40. https://doi.org/10.1186/s12935-017-0410-1

    Article  PubMed Central  PubMed  Google Scholar 

  • Yi JM, Huan XJ, Song SS, Zhou H, Wang YQ, Miao ZH (2016) Triptolide induces cell killing in multidrug-resistant tumor cells via CDK7/RPB1 rather than XPB or p44. Mol Cancer Ther 15:1495–1503

    Article  PubMed  CAS  Google Scholar 

  • Yip-Schneider MT, Wu H, Stantz K, Agaram N, Crooks PA, Schmidt CM (2013) Dimethylaminoparthenolide and gemcitabine: a survival study using a genetically engineered mouse model of pancreatic cancer. BMC Cancer 13:194. https://doi.org/10.1186/1471-2407-13-194

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Yogeeswari P, Sriram D (2005) Betulinic acid and its derivatives: a review on their biological properties. Curr Med Chem 12:657–666

    Article  PubMed  CAS  Google Scholar 

  • Yoshihara H, Yoshimoto Y, Hosoya Y, Hasegawa D, Kawano T, Sakoda A, Okita H, Manabe A (2017) Infantile fibrosarcoma treated with postoperative vincristine and dactinomycin. Pediatr Int 59:371–374

    Article  CAS  PubMed  Google Scholar 

  • Yu HJ, Ma L, Jiang J, Sun SQ (2016) Protective effect of curcumin on neural myelin sheaths by attenuating interactions between the endoplasmic reticulum and mitochondria after compressed spinal cord. J Spine 5:4. https://doi.org/10.4172/2165-7939.1000322

    Article  Google Scholar 

  • Yuan S, Wang L, Chen X, Fan B, Yuan Q, Zhang H, Yang D, Wang S (2016) Triptolide inhibits the migration and invasion of human prostate cancer cells via Caveolin-1/CD147/MMPs pathway. Biomed Pharmacother 84:1776–1782

    Article  CAS  PubMed  Google Scholar 

  • Zhang Q, Lu Y, Ding Y, Zhai J, Ji Q, Ma W, Yang M, Fan H, Long J, Tong Z, Shi Y, Jia Y, Han B, Zhang W, Qiu C, Ma X, Li Q, Shi Q, Zhang H, Li D, Zhang J, Lin J, Li LY, Gao Y, Chen Y (2012) Guaianolide sesquiterpene lactones, a source to discover agents that selectively inhibit acute myelogenous leukemia stem and progenitor cells. J Med Chem 55:8757–8769

    Article  CAS  PubMed  Google Scholar 

  • Zhang DM, Xu HG, Wang L, Li YJ, Sun PH, Wu XM, Wang GJ, Chen WM, Ye WC (2015) Betulinic acid and its derivatives as potential antitumor agents. Med Res Rev 35:1127–1155

    Article  CAS  PubMed  Google Scholar 

  • Zhang TJ, Han S, Zhang W, Zhao FJ, Li J (2016a) Triptolide promoting colon cancer CT26 cell death through induction of autophagy. Acta Anat Sin 47:774–778

    Google Scholar 

  • Zhang W, Kang M, Zhang T, Li B, Liao X, Wang R (2016b) Triptolide combined with radiotherapy for the treatment of nasopharyngeal carcinoma via NF-κB-related mechanism. Int J Mol Sci 17:2139. https://doi.org/10.3390/ijms17122139

    Article  PubMed Central  CAS  Google Scholar 

  • Zhang S, Wang S, Zhan J (2016c) Engineered biosynthesis of medicinally important plant natural products in microorganisms. Curr Top Med Chem 16:1740–1754

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Wen YL, Ma JW, Ye JC, Wang X, Huang JX, Meng CY, Xu XZ, Wang SX, Zhong XY (2017a) Tetrandrine inhibits glioma stem-like cells by repressing β-catenin expression. Int J Oncol 50:101–110

    Article  CAS  PubMed  Google Scholar 

  • Zhang PR, Zhang JH, Yu M, Zhang X (2017b) Triptolide reverses MCF-7/ADR cell resistance by down-regulating P-glycoprotein expression. Int J Clin Exp Med 10:1513–1521

    CAS  Google Scholar 

  • Zhao Y, Yang Y, Chen Q, Kasimu R, Akber Aisa H (2016a) Isolation of deoxypodophyllotoxin and podophyllotoxin from Juniperus sabina by high speed counter current chromatography. Afinidad 73:237–240

    CAS  Google Scholar 

  • Zhao L, Wu P, Zhang PG, Xie DZ, Gao D, Zhou NJ (2016b) Effect of triptolide on human colorectal cancer HCT116 cell proliferation, autophagy and apoptosis. Chin Pharmacol Bull 32:1399–1404

    Google Scholar 

  • Zhao G, Han X, Cheng W, Ni J, Zhang Y, Lin J, Song Z (2017) Apigenin inhibits proliferation and invasion, and induces apoptosis and cell cycle arrest in human melanoma cells. Oncol Rep 37:2277–2285

    Article  CAS  PubMed  Google Scholar 

  • Zhou ZL, Yang YX, Ding J, Li YC, Miao ZH (2012) Triptolide: structural modifications, structure–activity relationships, bioactivities, clinical development and mechanisms. Nat Prod Rep 29:457–475

    Article  CAS  PubMed  Google Scholar 

  • Zhou Z, Tang M, Liu Y, Zhang Z, Lu R, Lu J (2017) Apigenin inhibits cell proliferation, migration, and invasion by targeting Akt in the A549 human lung cancer cell line. Anti-Cancer Drugs 28:446–456

    Article  CAS  PubMed  Google Scholar 

  • Zhu W, Hu J, Wang X, Tian J, Komatsu S (2015) Organ-specific analysis of mahonia using gel-free/label-free proteomic technique. J Proteome Res 14:2669–2685

    Article  CAS  PubMed  Google Scholar 

  • Zong Y, Wu J, Shen K (2017) Nanoparticle albumin-bound paclitaxel as neoadjuvant chemotherapy of breast cancer: a systematic review and meta-analysis. Oncotarget 8:17360–17372

    PubMed Central  PubMed  Google Scholar 

  • Zulkipli IN, Rajabalaya R, Idris A, Sulaiman NA, David SR (2017) Clinacanthus nutans: a review on ethnomedicinal uses, chemical constituents and pharmacological properties. Pharm Biol 55:1093–1113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgement

Thanks are due to FCT/MEC for the financial support of the QOPNA research unit (FCT UID/QUI/00062/2013) and the cE3c centre (FCT UID/BIA/00329/2013) through national funds and, where applicable, co-financed by the FEDER, within the PT2020 Partnership Agreement.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Diana Cláudia Gouveia Alves Pinto .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Pinto, D.C.G.A., Seca, A.M.L., Silva, A.M.S. (2017). Insight Approaches of Medicinal Plants for the Discovery of Anticancer Drugs. In: Akhtar, M., Swamy, M. (eds) Anticancer Plants: Clinical Trials and Nanotechnology. Springer, Singapore. https://doi.org/10.1007/978-981-10-8216-0_4

Download citation

Publish with us

Policies and ethics