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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

General Review Article

Current Perspectives in the Application of Medicinal Plants Against Cancer: Novel Therapeutic Agents

Author(s): Sevgi Gezici* and Nazım Şekeroğlu

Volume 19 , Issue 1 , 2019

Page: [101 - 111] Pages: 11

DOI: 10.2174/1871520619666181224121004

Price: $65


Background: Cancer is a disease characterized by uncontrolled cell growth and proliferation. It has become a major health problem in the past decades and is now the second leading cause of death globally. Although, there are different types of treatment such as chemotherapy, immune therapy, radiation, hormone therapy and targeted therapy used against cancer, they have possible side effects and significant deficiencies.

Methods: This review aims to outline the benefits of medicinal plants and plant-derived products and highlight why they should be used as novel anti-cancer therapeutics. Electronic databases, including PubMed, Scopus, ScienceDirect, Cochrane library, and MedlinePlus were searched to summarize in vitro, in vivo and clinical studies on anticancer effects of medicinal plants and their bioactive compounds up-to-date.

Results: In recent years, a number of medicinal plants have been administered to cancer patients in order to prevent and treat cancer as an alternative therapy. These plants were used because of their rich anticarcinogenic and chemoprotective potentials. In addition to these remarkable properties, these plants have less toxic anticancer, anti-tumor and anti-proliferation agents than traditional therapeutics. Nevertheless, only a small number of natural anti-tumor products including vinblastine, vincristine, podophyllotoxin, paclitaxel (Taxol) and camptothecin have been tested clinically, while vinflunine ditartrate, anhydrovinblastine, NK-611, tafluposide, paclitaxel poliglumex, combretastatins, salvicine, curcumin, indirubin, triptolide, homoharringtonine are still on trial.

Conclusion: Consequently, more effective anticancer compounds are identified during the clinical trials; these natural products could be a key source of antitumor agents in modern anticancer therapy. It is expected that novel anticancer phytopharmaceuticals produced from medicinal plants could be effectively used in prevention and therapy for the cancers.

Keywords: Anti-cancer agents, cancer, herbal medicine, natural products, medicinal plants, phyto-pharmaceuticals.

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Pan, L.; Chai, H.; Kinghorn, A.D. The continuing search for antitumor agents from higher plants. . Phytochem. Lett., 2010, 3, 1-8.
Song, M.; Vogelstein, B.; Giovannucci, E.L.; Willett, W.C.; Tomasetti, C. Cancer prevention: Molecular and epidemiologic consensus. Science, 2018, 361(6409), 1317-1318.
American cancer society, global cancer facts and figures. American Cancer Society, Atlanta 2018. Available at. research/cancerfactsstatistics/global
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics. CA Cancer J. Clin., 2018, 68, 7-30.
Balunas, M.J.; Kinghorn, D. Drug discovery from medicinal plants. Life Sci., 2005, 78, 431-441.
Tan, B.L.; Norhaizan, M.E. Plant-Derived Compounds in Cancer Therapy: Traditions of Past and Drugs of Future. In. Anticancer plants: Properties and Application, 2018, 91-127. Springer, Singapore.
Tagne, R.S.; Telefo, B.P.; Nyemb, J.N.; Yemele, D.M.; Nijina, S.N.; Chekem-Goka, S.M.; Lienou, L.L.; Nwabo-Kambdje, A.H.; Moundipa, P.F.; Farooq, A.D. Anticancer and antioxidant activities of methanol extracts and fractions of some Cameroonian medicinal plants. Asian Pac. J. Trop. Med., 2014, 7, 442-447.
Levitsky, D.O.; Dembitsky, V.M. Anti-breast cancer agents derived from plants. Nat. Prod. Bioprospect., 2015, 5, 1-16.
Dipaola, R.S.; Zhang, H.; Lambert, G.H.; Meeker, R.; Licitra, E.; Rafi, M.M.; Zhu, B.T.; Spaulding, H.; Goodin, S.; Toledano, M.B.; Hait, W.N.; Gallo, M.A. Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer. N. Engl. J. Med., 1998, 339, 785-791.
Cragg, G.M.; Newman, D.J. Plants as a source of anti-cancer agents. J. Ethnopharmacol., 2005, 100, 72-79.
Reddy, L.; Odhav, B.; Bhoola, K.D. Natural products for cancer prevention: A global perspective. Pharmacol. Ther., 2003, 99, 1-13.
Mishra, B.B.; Tiwari, V.K. Natural products: An evolving role in future drug discovery. Eur. J. Med. Chem., 2011, 46, 4769-4807.
Ahmed, M.; Khan, M.I.; Khan, M.R.; Muhammad, N.; Khan, A.U.; Khan, R.A. Role of medicinal plants in oxidative stress and cancer. Open Acc. Sci. Rep., 2013, 2, 641-643.
Teiten, M.H.; Gaascht, F.; Dicato, M.; Diederich, M. Anticancer bioactivity of compounds from medicinal plants used in European medieval traditions. Biochem. Pharmacol., 2013, 86, 1239-1247.
Nguta, J.M.; Appiah-Opong, R.; Nyarko, A.K.; Yeboah-Manu, D.; Addo, P.G.A. Medicinal plants used to treat TB in Ghana. Int. J. Mycobacteriol., 2015, 4, 116-123.
Roleira, F.M.; Varela, C.L.; Costa, S.C.; Tavares-da-Silva, E.J. Phenolic derivatives from medicinal herbs and plant extracts: anticancer effects and synthetic approaches to modulate biological activity. Stud. Nat. Prod. Chem., 2018, 57, 115-156.
Rashed, K.N. Medicinal plants as a safe target for treatment of cancer. Nat. Prod. Chem. Res., 2014, 2, 6836.
Seca, A.; Pinto, D. Plant secondary metabolites as anticancer agents: Successes in clinical trials and therapeutic application. Int. J. Mol. Sci., 2018, 19(1), 263.
Dhanamani, M.; Devi, L.S.; Kannan, S. Ethnomedicinal plants for cancer therapy-A review. Hygeia J. D. Med., 2011, 3, 1-10.
Friedberg, E.C.; Walker, G.C.; Siede, W.; Wood, R.D.; Schultz, R.A.; Ellenberger, T. DNA repair and mutagenesis. 2006, 2nd edition, ASM Press.
Sarasin, A. An overview of the mechanisms of mutagenesis and carcinogenesis. Mutat. Res. Fundam. Mol. Mech. Mutagen., 2003, 544, 99-106.
Heinen, C.D.; Schmutte, C.; Fishel, R. DNA repair and tumorigenesis: lessons from hereditary cancer syndromes. Cancer Biol. Ther., 2002, 1, 477-485.
Wood, R.D.; Mitchell, M.; Lindahl, T. Human DNA repair genes. Mutat. Res. Fundam. Mol. Mech. Mutagen., 2005, 577, 275-283.
Banning, M. The carcinogenic and protective effects of food. Br. J. Nurs., 2005, 14, 1070-1074.
Vickers, A. Botanical medicines for the treatment of cancer: rationale, overview of current data, and methodological considerations for phase I and II trials. Cancer Invest., 2002, 20, 1069-1079.
Bonham, M.; Arnold, H.; Montgomery, B.; Nelson, P.S. Molecular effects of the herbal compound PC-SPES: Identification of activity pathways in prostate carcinoma. Cancer Res., 2002, 62, 3920-3924.
Hu, H.; Ahn, N.S.; Yang, X.; Lee, Y.S.; Kang, K.S. Ganoderma lucidum extract induces cell cycle arrest and apoptosis in MCF-7 human breast cancer cell. Int. J. Cancer, 2002, 102, 250-253.
Twilley, D.; Lall, N. The role of natural products from plants in the development of anticancer agentS; Nat. Products Drug Dis, 2018, pp. 139-178.
Cassady, J.M.; Douros, J.D. (Eds.). Anticancer agents based on natural product models Academic Press, 1980, New York.
Kaefer, C.M.; Milner, J.A. The role of herbs and spices in cancer prevention. J. Nutr. Biochem., 2008, 19, 347-361.
Mamedov, N. Medicinal plants studies: History, challenges and prospective. Med. Aromat. Plants, 2012, 1, 1-2.
Harun-ur-Rashid, M.D.; Gafur, M.A.; Sadik, M.G.; Rahman, M.A.A. Biological activities of a new acrylamide derivative from Ipomoea turpethum. Pak. J. Biol. Sci., 2002, 5, 968-969.
Sala, A.; Recio, M.; Giner, R.M.; Máñez, S.; Tournier, H.; Schinella, G. Anti-inflammatory and antioxidant properties of Helichrysum italicum. J. Pharm. Pharmacol., 2002, 54, 365-371.
Siriwatanametanona, N.; Fiebich, B.L.; Efferth, T.; Prietoa, J.M.; Heinricha, M. Traditionally used Thai medicinal plants: In vitro anti-inflammatory, anticancer and antioxidant activities. J. Ethnopharmacol., 2010, 130, 196-207.
Kaur, R.; Kapoor, K.; Kaur, H. Plants as a source of anticancer agents. J. Nat. Prod. Plant Resour., 2011, 1, 119-124.
Fabricant, D.S.; Farnsworth, N.R. The value of plants used in traditional medicine for drug discovery. Environ. Health Perspect., 2001, 109, 69-75.
Simmons, T.L.; Andrianasolo, E.; McPhail, K. Marine natural products as anticancer drugs. Mol. Cancer Ther., 2005, 4, 333-342.
Ajumeera, R.; Thipparapu, G.; Challa, S. Remedy of Targeting Cancer and Cancer Stem Cells with Botanicals. In. Anticancer Plants: Natural Products and Biotechnological Implements., 2018, 289-320. Springer, Singapore.
Marris, E. Marine natural products: Drugs from the deep. Nature, 2006, 443, 904-905.
Chen, H.; Gao, Y.; Wang, A.; Zhou, X.; Zheng, Y.; Zhou, J. Evolution in medicinal chemistry of ursolic acid derivatives as anticancer agents. Eur. J. Med. Chem., 2015, 92, 648-655.
Newman, D.J.; Cragg, G.M.; Sanader, K.M. Natural products as sources of new drugs over the period 1981-2002. J. Nat. Prod., 2003, 66, 1022-1037.
El-Shemy, H.A.; Aboul-Enein, A.M.; Aboul-Enein, M.I.; Issa, S.I.; Fujita, K. The effect of willow leaf extracts on human leukemic cells in vitro. J. Biochem. Mol. Biol., 2003, 36, 387-389.
Yano, H.; Mizoguchi, A.; Fukuda, K.; Haramaki, M.; Ogasawara, S. The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1 phase. Cancer Res., 1994, 54, 448-454.
Poma, A.; Miranda, M.; Spanò, L. Differential response of human melanoma and Ehrlich ascites cells in vitro to the ribosome-inactivating protein luffin. Melanoma Res., 1998, 8, 465-467.
Dong, Y.; Yang, M.M.; Kwan, C.Y. In vitro inhibition of proliferation of HL-60 cells by tetrandrine and Coriolus versicolor peptide derived from Chinese medicinal herbs. Life Sci., 1997, 60, 135-140.
Kagiki, F.O.; Goncalves, G.C.; Oliveira, E.T.; Crocomo, O.J.; Gallo, L.A. Callus induction and production of total saponins in Pfaffia glomerata (Spreng.) Pedersen in vitro. Braz. J. Med. Plants, 2004, 7, 43-50.
Fontanive, T.O.; Kobayashi, C.; Bona, L.R.; Massoni, T.; Weizenmann, M.; Tasca, T.; Gamaro, G.D.; Maluf, R.W.; Picoli, S.U.; Ardenghi, P.; Suyenaga, E.S. Evaluation of the pharmacological activity of Pfaffia paniculata (Martius). Kuntze. Lat. Am. J. Pharm., 2010, 29, 64-71.
Kaileh, M.; Berghe, W.V.; Boone, E.; Essawi, T.; Haegeman, G. Screening of indigenous Palestinian medicinal plants for potential anti-inflammatory and cytotoxic activity. J. Ethnopharmacol., 2010, 113, 510-516.
Bachrach, Z.Y. Contribution of selected medicinal plants for cancer prevention and therapy. Sci. J. Facul. Med. Nis., 2012, 29, 117-123.
Sartippour, M.R.; Pietras, R.; Marquez-Garban, D.C.; Chen, H.W.; Heber, D.; Henning, S.M.; Brooks, M.N. The combination of green tea and tamoxifen is effective against breast cancer. Carcinogenesis, 2006, 27, 2424-2433.
Myung, S.K.; Bae, W.K.; Oh, S.M.; Kim, Y.; Ju, W.; Sung, J.; Choi, H.J. Green tea consumption and risk of stomach cancer: A meta‐analysis of epidemiologic studies. Int. J. Cancer, 2009, 124, 670-677.
Hakimuddin, F.; Paliyath, G.; Meckling, K. Selective cytotoxicity of a red grape wine flavonoid fraction against MCF-7 cells. Breast Cancer Res. Treat., 2004, 85, 65-79.
Pezzuto, J.M.; Kondratyuk, T.P.; Shalaev, E. Chemoprevention by wine polyphenols and resveratrol. Carcinog. Anticarcinog. Food Comp., 2005, 96, 239-242.
Yedjou, C.; Izevbigie, E.; Tchounwou, P. Preclinical assessment of Vernonia amygdalina leaf extracts as DNA damaging anti-cancer agent in the management of breast cancer. Int. J. Environ. Res. Public Health, 2008, 5, 337-341.
Oyugi, D.A.; Luo, X.; Lee, K.S.; Hill, B.; Izevbigie, E.B. Activity markers of the anti-breast carcinoma cell growth fractions of Vernonia amygdalina extracts. Exp. Biol. Med., 2009, 234, 410-417.
Amr, N.A.; Ahmed, A.E.; Khalid, A.E.; David, A.L.; Alan, C. Anti-cancer and antioxidant activity of some Egyptian medicinal plants. J. Med. Plants Res., 2009, 3, 799-808.
Lu, N.; Zhang, S.; Ge, Q.A. Medicine for the treatment of breast carcinoma. 2002, Faming Zhuanli Shenqing Gongkai Shuomingshu Patent CN 1371711.
Samarghandian, S.; Boskabady, M.H.; Davoodi, S. Use of in vitro assays to assess the potential anti-proliferative and cytotoxic effects of saffron (Crocus sativus L.) in human lung cancer cell line. Pharmacogn. Mag., 2010, 24, 309-314.
Gutheil, W.G.; Reed, G.; Ray, A.; Anant, S.; Dhar, A. Crocetin: An agent derived from saffron for prevention and therapy for cancer. Curr. Pharm. Biotechnol., 2012, 31, 173-179.
Ohyama, K.; Akaike, T.; Hirobe, C.; Yamakawa, T. Cytotoxicity and apoptotic inducibility of Vitex agnus-castus fruit extract in cultured human normal and cancer cells and effect on growth. Biol. Pharm. Bull., 2003, 26, 10-18.
Conforti, F.; Ioele, G.; Statti, G.A.; Marrelli, M.; Ragno, G.; Menichini, F. Anti-proliferative activity against human tumor cell lines and toxicity test on mediterranean dietary plants. Food Chem. Toxicol., 2008, 46, 3325-3332.
Agarwal, C.; Sharma, Y.; Agarwal, R. Anti-carcinogenic effect of a polyphenolic fraction isolated in human prostate carcinoma DU145 cells: Modulation of cell cycle regulators and induction of G1 arrest. Mol. Carcinog., 2000, 28, 129-138.
Zhang, Z.; Liong, E.C.; Lau, T.Y.; Leung, K.M.; Fung, P.C.; Tipoe, G.L. Induction of apoptosis by hexamethylene bisacetamide is p53-dependent with telomerase activity but not with terminal differentiation. Int. J. Oncol., 2000, 16, 887-892.
Van-Huyen, D.J.P.; Sooryanarayana, V.; Delignat, S.; Bloch, M.F.; Kazatchkine, M.D.; Kaveri, S.V. Variable sensitivity of lymphoblastoid cells to apoptosis induced by Viscum album Qu FrF, a therapeutic preparation of mistletoe lectin. Chemotherapy, 2001, 47, 366-376.
Hecht, S.S.; Kenney, P.M.; Wang, M.; Trushin, N.; Agarwal, S.; Rao, A.V.; Upadhyaya, P. Evaluation of butylated hydroxyanisole, myo-inositol, curcumin, esculetin, resveratrol, and lycopene as inhibitors of benzo[a]pyrene plus 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanoneinduced lung tumorigenesis in A/J mice. Cancer Lett., 1999, 137, 123-130.
Nakahata, N.; Kutsuwa, M.; Kyo, R.; Kubo, M.; Hayashi, K.; Ohizumi, Y. Analysis of inhibitory effects of Scutellariae radix and baicalein on prostaglandin E2 production in rat C6 glioma cells. Am. J. Chin. Med., 1998, 26, 311-323.
Polkowski, K.; Mazurek, A.P. Biological properties of genistein. A review of in vitro and in vivo data. Acta Pol. Pharm., 2000, 57, 135-155.
Zheng, S.; Yang, H.; Zhang, S.; Wang, X.; Yu, L.; Lu, J.; Li, J. Initial study on naturally occurring products from traditional Chinese herbs and vegetables for chemoprevention. J. Cell. Biochem., 1997, 67, 106-112.
Eberhardt, M.V.; Lee, C.Y.; Lui, R.H. Antioxidant activity of fresh apples. Nature, 2000, 405, 903-904.
Cheng, Y.H.; Shen, T.F.; Pang, V.F.; Chen, B.J. Effects of aflatoxin and carotenoids on growth performance and immune response in mule ducklings. Comp. Biochem. Physiol. Part-C Toxicol. Pharmacol., 2001, 128, 19-26.
Cardador-Martinez, A.; Casttano-Tostado, E.; Loarea-Pina, G. Antimutagenic activity of natural phenolic compounds present the common bean (Phaseolus vulgaris) against aflatoxin B1. Food Addit. Contam., 2002, 19, 62-69.
Harvey, A.L. Natural products in drug discovery. Drug Discov. Today, 2008, 13, 894-901.
DeVita, V.T.; Hellman, S.; Rosenberg, S.A. (Eds.), Cancer: Principles and practice of oncology. 2008, 8th Ed. Lippincott-Williams & Wilkins, Philadelphia.
Svoboda, G.H.; Neuss, N.; Gorman, M. Alkaloids of Vinca rosea Linn. (Catharanthus roseus G. Don.) V. Preparation and characterization of alkaloids. J. Am. Pharm. Assoc., 1959, 48, 659-666.
Gordaliza, M. Natural products as leads to anticancer drugs. Clin. Transl. Oncol., 2007, 9, 767-776.
Wani, M.C.; Taylor, H.L.; Wall, M.E.; Coggon, P.; McPhail, A.T. Plant antitumor agents. VI. Isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J. Am. Chem. Soc., 1971, 93, 2325-2327.
Johnson, I.S. Historical background of Vinca alkaloids research and areas of future interest. Cancer Chemother. Rep. Part 1, 1968, 52, 455-461.
Efferth, T.; Li, P.C.; Konkimalla, V.S.B.; Kaina, B. From traditional Chinese medicine to rational cancer therapy. Trends Mol. Med., 2007, 13, 353-361.
Wall, M.E.; Wani, M.C. Camptothecin and taxol: Discovery to clinic-thirteenth Bruce F. Cain Memorial Award Lecture. Cancer Res., 1995, 55, 753-760.
Ding, Y.F.; Bao, Y.M.; An, L.J. Progress research of antitumor agents’ vinblastine analogues. Chin. J. Pharm., 2005, 36, 424.
Mano, M. Vinorelbine in the management of breast cancer: New perspectives, revived role in the era of targeted therapy. Cancer Treat. Rev., 2006, 32, 106-118.
You, J.; Wan, F.; de-Cui, F.; Sun, Y.; Du, Y.Z.; Hu, Q.F. Preparation and characteristic of vinorelbine bitartrate-loaded solid lipid nanoparticles. Int. J. Pharm., 2007, 343, 270-276.
Ferlini, C.; Ojima, I.; Distefano, M.; Gallo, D.; Riva, A.; Morazzoni, P.; Scambia, G. Second generation taxanes: From the natural framework to the challenge of drug resistance. Curr. Med. Chem. Anticancer Agents, 2003, 3, 133-138.
Nicolaou, K.C.; Yang, Z.; Liu, J.J.; Ueno, H.; Nantermet, P.G.; Guy, R.K.; Sorensen, E.J. Total synthesis of taxol. Nature, 1994, 367, 630-634.
Kingston, D.G.; Newman, D.J. Taxoids: Cancer-fighting compounds from nature. Curr. Opin. Drug Discov. Devel., 2007, 10, 130-144.
Kuznetsova, L.; Chen, J.; Sun, L.; Wu, X.; Pepe, A.; Veith, J.M.; Pera, P.; Bernacki, R.J.; Ojima, I. Syntheses and evaluation of novel fatty acid-second- generation taxoid conjugates as promising anticancer agents. Bioorg. Med. Chem. Lett., 2006, 16, 974-977.
Nakagawa-Goto, K.; Yamada, K.; Nakamura, S.; Chen, T.H.; Chiang, P.C.; Bastow, F.K. Antitumor agents. 258. Syntheses and evaluation of dietary antioxidant-taxoid conjugates as novel cytotoxic agents. Bioorg. Med. Chem. Lett., 2007, 17, 5204-5209.
Wall, M.E.; Wani, M.C. Camptothecin and taxol: From discovery to clinic. J. Ethnopharmacol., 1996, 51, 239-254.
Kingston, D.G.I.; Bane, S.; Snyder, J.P. The taxol pharmacophore and the T-taxol bridging principle. Cell Cycle, 2005, 4, 279-289.
Malonga, H.; Neault, J.F.; Diamantoglou, S.; Tajmir-Riahi, H.A. Taxol anticancer activity and DNA binding. Mini Rev. Med. Chem., 2005, 5, 307-311.
Utsugi, T.; Shibata, J.; Sugimoto, Y.; Aoyagi, K.; Wierzba, K.; Kobunai, T. Antitumor activity of a novel podophyllotoxin derivative (TOP-53) against lung cancer and lung metastatic cancer. Cancer Res., 1996, 56, 2809-2814.
Subrahmanyam, D.; Renuka, B.; Rao, C.V.; Sagar, P.S.; Deevi, S.D.; Babu, J.M.; Vyas, K. Novel D-ring analogues of podophyllotoxin as potent anti-cancer agents. Bioorg. Med. Chem. Lett., 1998, 8, 1391-1396.
Stahelin, H.; VonWartburg, A. From podophyllotoxin glucoside to etoposide. Prog. Drug Res., 1989, 33, 169-266.
Von-Wartburg, A.; Stähelin, H. Etoposide. In: Lednicer D (Ed.) Chronicles of Drug Discovery. American Chemical Society, 1993, Washington DC.
Meresse, P.; Dechaux, E.; Monneret, C.; Bertounesque, E. Etoposide: Discovery and medicinal chemistry. Curr. Med. Chem., 2004, 11, 2443-2466.
Hartmann, J.T.; Lipp, H.P. Camptothecin and podophyllotoxin derivatives: Inhibitor of topoisomerase I and II - mechanism of action, pharmacokinetics and toxicity profile. Drug Saf., 2006, 29, 209-230.
Cersisimo, R.J. Irinotecan: A new antineoplastic agent for the management of colorectal cancer. Ann. Pharmacother., 1998, 32, 1324-1333.
Malonne, H.; Atassi, G. DNA topoisomerase targeting drugs: mechanisms of action and perspectives. Anticancer Drugs, 1997, 8, 811-822.
Carbonero, G.R.; Supko, J.G. Current perspectives on the clinical experience, pharmacology and continued development of the camptothecins. Clin. Cancer Res., 2002, 8, 641-661.
Tietze, L.F.; Bell, H.P.; Chandrasekhar, S. Natural product hybrids as new leads for drug discovery. Angew. Chem. Int. Ed., 2003, 42, 3996-4028.
Busquets, S.; Ametller, E.; Fuster, G.; Olivan, M.; Raab, V.; Argilés, J.M.; López-Soriano, F.J. Resveratrol, a natural diphenol, reduces metastatic growth in an experimental cancer model. Cancer Lett., 2007, 245, 144-148.
White, S.J.; Kasman, L.M.; Kelly, M.M.; Lu, P.; Spruill, L. Doxorubicin generates a proapoptotic phenotype by phosphorylation of elongation factor 2. Free Radic. Biol. Med., 2007, 43, 1313-1321.
Corson, T.W.; Crews, C.M. Molecular understanding and modern application of traditional medicines: Triumphs and trials. Cell, 2007, 130, 769-774.
Butler, M.S. Natural products to drugs: Natural product-derived compounds in clinical trials. Nat. Prod. Rep., 2008, 25, 475-416.
Saklani, A.; Kutty, S.K. Plant-derived compounds in clinical trials. Drug Discov. Today, 2008, 13, 161-171.
Kiviharju, T.M.; Lecane, P.S.; Sellers, R.G.; Peehl, D.M. Anti-proliferative and proapoptotic activities of triptolide (PG490), a natural product entering clinical trials, on primary cultures of human prostatic epithelial cells. Clin. Cancer Res., 2002, 8, 2666-2674.
Fidler, J.M.; Li, K.; Chung, C.; Wei, K.; Ross, J.A.; Gao, M.; Rosen, G.D. PG490-88, a derivative of triptolide, causes tumor regression and sensitizes tumors to chemotherapy. Mol. Cancer Ther., 2003, 2, 855-862.
Raynal, N.J.M.; Momparler, L.; Charbonneau, M.; Momparler, R.L. Antileukemic activity of genistein, a major isoflavone present in soy products. J. Nat. Prod., 2008, 71, 3-7.
Liu, G.Y.; Bu, X.; Yan, H.; Jia, W.W.G. 20S-Protopanaxadiol-induced programmed cell death in glioma cells through caspase-dependent and -independent pathways. J. Nat. Prod., 2007, 70, 259-265.
Pettit, G.R.; Singh, S.B.; Niven, M.L.; Hamel, E.; Schmidt, J.M. Isolation, structure, and synthesis of combretastatins A-1 and B-1, potent new inhibitors of tubulin assembly, derived from Combretum caffrum. J. Nat. Prod., 1987, 50, 119-131.
Delmonte, A.; Sessa, C. AVE8062: A new combretastatin derivative vascular disrupting agent. Expert Opin. Investig. Drugs, 2009, 18, 1541-1548.
Pisha, E.; Chai, H.; Lee, I.S.; Chagwedera, T.E.; Farnsworth, N.R.; Cordell, G.A.; Beecher, C.W.W.; Fong, H.H.S.; Kinghorn, A.D.; Brown, D.M.; Wani, M.C.; Wall, M.E.; Heijken, T.E.; Gupta, D.T.K.; Pezzuto, J.M. Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nat. Med., 1995, 1, 1046-1051.
Zhang, J.S.; Ding, J.; Tang, Q.M.; Li, M.; Zhao, M.; Lu, L.J.; Chen, L.J.; Yuan, S.T. Synthesis and antitumor activity of novel diterpenequinone salvicine and the analogs. Bioorg. Med. Chem. Lett., 1999, 9, 2731-2736.
Cai, Y.J.; Lu, J.J.; Zhu, H.; Xie, H.; Huang, M.; Lin, L.P.; Zhang, X.W.; Ding, J. Salvicine triggers DNA double-strand breaks and apoptosis by GSH-depletion driven H2O2 generation and topoisomerase II inhibition. Free Radic. Biol. Med., 2008, 45, 6227-6235.
Aggarwal, B.B.; Sundaram, C.; Malani, N.; Ichikawa, H. Curcumin: The Indian solid gold. Adv. Exp. Med. Biol., 2007, 595, 1-75.
Dhillon, N.; Aggarwal, B.B.; Newman, R.A.; Wolff, R.A.; Kunnumakkara, A.B.; Abbruzzese, J.L.; Ng, C.S.; Badmaev, V.; Kurzrock, R. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin. Cancer Res., 2008, 14, 4491-4499.
Eisenbrand, G.; Hippe, F.; Jakobs, S.; Muehlbeyer, S. Molecular mechanisms of indirubin and its derivatives: Novel anticancer molecules with their origin in traditional Chinese phytomedicine. J. Cancer Res. Clin. Oncol., 2004, 130, 627-635.
Itokawa, H.; Wang, X.; Lee, K.H. Homoharringtonine and related compounds. In: Cragg GM, Kingston DGI, Newman DJ. (Eds.), Anticancer Agents from Natural Products, 2005, CRC/Taylor & Francis, Boca Raton, FL.
Quintás‐Cardama, A.; Kantarjian, H.; Garcia‐Manero, G.; O’brien, S.; Faderl, S.; Estrov, Z.; Giles, F.; Murgo, A.; Ladie, N.; Verstovsek, S.; Cortes, J. Phase I/II study of subcutaneous homoharringtonine in patients with chronic myeloid leukemia who have failed prior therapy. Cancer, 2007, 109, 248-255.
Wright, J.; Blatner, G.L.; Cheson, B.D. Clinical trials referral resource. Clinical trials of flavopiridol. Oncology, 1998, 12, 1023-1024.
Meijer, L.; Raymond, E. Roscovitine and other purines as kinase inhibitors. From starfish oocytes to clinical trials. Acc. Chem. Res., 2003, 36, 417-425.
Powell, R.G.; Weisleder, D.; Smith, C.R. Antitumor alkaloids from Cephalotaxus harringtonia: structure and activity. J. Pharm. Sci., 1972, 61, 1227-1230.
Pinney, K.G.; Jelinek, C.; Edvardsen, K.; Chaplin, D.J.; Pettit, G.R. The discovery and development of the combretastatins. In:. Cragg GM, Kingston DGI, Newman DJ. (Eds.), Anticancer Agents from Natural Products, 2005, CRC Taylor & Francis, Boca Raton, FL.
Penthala, N.R.; Thakkar, S.; Crooks, P.A. Heteroaromatic analogs of the resveratrol analog DMU-212 as potent anti-cancer agents. Bioorg. Med. Chem. Lett., 2015, 25, 2763-2767.
Miao, Z.H.; Tang, T.; Zhang, Y.X.; Zhang, J.S.; Ding, J. Cytotoxicity, apoptosis induction and downregulation of MDR-1 expression by the anti-topoisomerase II agent, salvicine, in multidrug-resistant tumor cells. Int. J. Cancer, 2003, 106, 108-115.
Cooperative Study Group of Phase III Clinical Trial on Meisoindigo. Phase II clinical trial on meisoindigo in the treatment of chronic myelogenous leukemia. Zhonghua Xueyexue Zazhi, 1997, 18, 69-72.
Johnson, J.J.; Mukhtar, H. Curcumin for chemoprevention of colon cancer. Cancer Lett., 2007, 255, 170-181.
Dai, F.; Liu, G.Y.; Li, Y.; Yan, W.J.; Wang, Q.; Yang, J.; Lu, D.L.; Ding, D.J.; Lin, D.; Zhou, B. Insights into the importance for designing curcumin-inspired anticancer agents by a prooxidant strategy: The case of diarylpentanoids. Free Radic. Biol. Med., 2015, 85, 127-137.
PanaGin Pharmaceuticals Ins., 2009. Further information Available at. http//
Senderowicz, A.M.; Headlee, D.; Stinson, S.F.; Lush, R.M.; Kalil, N.; Villalba, L.; Hill, K.; Steinberg, S.M.; Figg, W.D.; Tompkins, A. Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms. J. Clin. Oncol., 1998, 2986-2999.
Mottamal, M.; Zheng, S.; Huang, T.L.; Wang, G. Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules, 2015, 20(3), 3898-3941.
Nosrati, N.; Bakovic, M.; Paliyath, G. Molecular mechanisms and pathways as targets for cancer prevention and progression with dietary compounds. Int. J. Mol. Sci., 2017, 18(10), 2050.
Wang, H.; O’Khor, T.; Shu, L.; Su, Z.Y.; Fuentes, F.; Lee, J.H.; Kong, T.A.N. Plants vs cancer: A review on natural phytochemicals in preventing and treating cancers and their drug ability. Anticancer. Agents Med. Chem., 2012, 12(10), 1281-1305.

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