Cancer chemoprevention through the induction of apoptosis by natural compounds


As cell and tissue homeostasis are mediated by the balance between proliferation and apoptosis, controlling this balance is important for cancer chemoprevention. Cancer chemoprevention can be achieved by the use of natural, synthetic or biologic compounds that reverse, suppress or prevent the development of epithelial malignancies. Natural compounds including flavonoids are able to reduce oxidative stress, which is the most likely mechanism mediating the protective effects against cancer development. In addition, in vitro and in vivo studies have suggested that flavonoids, such as (-)-epigallocatechin-3-gallete (EGCG), quercetin, and curcumin, act by induction of apoptosis. Several natural compounds inhibit cell proliferation and angiogenesis. Certain natural products have been shown to inhibit the activation of nuclear factor kappa B (NF-κB) and Akt signaling pathways, both of which are known to maintain a homeostatic balance between cell survival and apoptosis. Understanding the mechanism of these natural products will contribute to the development of more specific preventive strategies against cancer development. Here we focus on the ability of natural cancer chemopreventive agents to induce apoptosis, and attempt to provide evidence for the preventive and therapeutic effects of natural compounds, EGCG, quercetin, and curcumin, in a succinct manner highlightingκand Akt signaling pathways in vivo.

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Kuno, T. , Tsukamoto, T. , Hara, A. and Tanaka, T. (2012) Cancer chemoprevention through the induction of apoptosis by natural compounds. Journal of Biophysical Chemistry, 3, 156-173. doi: 10.4236/jbpc.2012.32018.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Donaldson, M.S. (2004) Nutrition and cancer: A review of the evidence for an anti-cancer diet. Nutrition Journal, 3, 19. doi:10.1186/1475-2891-3-19
[2] Riboli, E. and Norat, T. (2003) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk. American Journal of Clinical Nutrition, 78, 559S-569S.
[3] Gonzalez, C.A. and Riboli, E. (2006) Diet and cancer prevention: Where we are, where we are going. Nutrition and Cancer, 56, 225-231. doi:10.1207/s15327914nc5602_14
[4] Nichenametla, S.N., Taruscio, T.G., Barney, D.L. and Exon, J.H. (2006) A review of the effects and mechanisms of polyphenolics in cancer. Critical Reviews in Food Science and Nutrition, 46, 161-183. doi:10.1080/10408390591000541
[5] Ramos, S. (2008) Cancer chemoprevention and chemotherapy: Dietary polyphenols and signalling pathways. Molecular Nutrition and Food Research, 52, 507-526. doi:10.1002/mnfr.200700326
[6] Lambert, J.D. Hong, J., Yang, G.Y., Liao, J. and Yang, C.S. (2005) Inhibition of carcinogenesis by polyphenols: Evidence from laboratory investigations. American Journal of Clinical Nutrition, 81, 284S-291S.
[7] Fresco, P., Borges, F., Diniz, C. and Marques, M.P. (2006) New insights on the anticancer properties of dietary polyphenols. Medical Research Reviews, 26, 747-766. doi:10.1002/med.20060
[8] Sun, S.Y., Hail, N. Jr. and Lotan, R. (2004) Apoptosis as a novel target for cancer chemoprevention. Journal of National Cancer Institute, 96, 662-672. doi:10.1093/jnci/djh123
[9] Martin, K.R. (2006) Targeting apoptosis with dietary bioactive agents. Experimental Biolology and Medicine (Maywood), 231, 117-129.
[10] Hail, N. Jr. (2005) Mitochondria: A novel target for the chemoprevention of cancer. Apoptosis: An International Journal on Programmed Cell Death, 10, 687-705. doi:10.1007/s10495-005-0792-8
[11] Hail, N. Jr., Cortes, M., Drake, E.N. and Spallholz, J.E. (2008) Cancer chemoprevention: A radical perspective. Free Radical Biology and Medicine, 45, 97-110. doi:10.1016/j.freeradbiomed.2008.04.004
[12] Manach, C., Williamson, G., Morand, C., Scalbert, A. and Remesy, C. (2005) Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. American Journal of Clinical Nutrition, 81, 230S-242S.
[13] Scalbert, A., Manach, C., Morand, C., Remesy, C. and Jimenez, L. (2005) Dietary polyphenols and the prevention of diseases. Critical Reviews in Food Science and Nutrition, 45, 287-306. doi:10.1080/1040869059096
[14] Watson, W.H., Cai, J. and Jones, D.P. (2000) Diet and apoptosis. Annual Review of Nutrition, 20, 485-505. doi:10.1146/annurev.nutr.20.1.485
[15] Riboli, E., Norat, T. (2001) Cancer prevention and diet: Opportunities in Europe. Public Health Nutrition, 4, 475-484. doi:10.1079/PHN2001158
[16] Stan, S.D., Kar, S., Stoner, G.D. and Singh, S.V. (2008) Bioactive food components and cancer risk reduction. Jpournal of Cellular Biochemistry, 104, 339-356. doi:10.1002/jcb.21623
[17] Lepley, D.M., Li, B., Birt, D.F. and Pelling, J.C. (1996) The chemopreventive flavonoid apigenin induces G2/M arrest in keratinocytes. Carcinogenesis, 17, 2367-2375. doi:10.1093/carcin/17.11.2367
[18] Skaper, S.D., Fabris, M., Ferrari, V., Dalle Carbonare, M. and Leon, A. (1997) Quercetin protects cutaneous tissueassociated cell types including sensory neurons from oxidative stress induced by glutathione depletion: Cooperative effects of ascorbic acid. Free Radical Biology and Medicine, 22, 669-678. doi:10.1016/S0891-5849(96)00383-8
[19] Agullo, G., Gamet-Payrastre, L., Manenti, S., Viala, C., Remesy, C., Chap, H. and Payrastre, B. (1997) Relationship between flavonoid structure and inhibition of phosphatidylinositol 3-kinase: A comparison with tyrosine kinase and protein kinase C inhibition. Biochemical Pharmacology, 53, 1649-1657. doi:10.1016/S0006-2952(97)82453-7
[20] Sergediene, E., Jonsson, K., Szymusiak, H., Tyrakowska, B., Rietjens, I.M. and Cenas, N. (1999) Prooxidant toxicity of polyphenolic antioxidants to HL-60 cells: Description of quantitative structure-activity relationships. FEBS Letters, 462, 392-396. doi:10.1016/S0014-5793(99)01561-6
[21] Bianco, A.D., Muzzalupo, I., Piperno, A., Romeo, G. and Uccella, N. (1999) Bioactive derivatives of oleuropein from olive fruits. Journal of Agricultural and Food Chemistry, 47, 3531-3534. doi:10.1021/jf981240p
[22] Hollman, P.C. and Katan, M.B. (1999) Dietary flavonoids: Intake, health effects and bioavailability. Food and Chemical Toxicology, 37, 937-942. doi:10.1016/S0278-6915(99)00079-4
[23] Visioli, F. and Galli, C. (2002) Biological properties of olive oil phytochemicals. Critical Reviews in Food Science and Nutrition, 42, 209-221. doi:10.1080/10408690290825529
[24] Scalbert, A. and Williamson, G. (2000) Dietary intake and bioavailability of polyphenols. Journal of Nutrition, 130, 2073S-2085S.
[25] Higdon, J.V. and Frei, B. (2003) Tea catechins and polyphenols: Health effects, metabolism, and antioxidant functions. Critical Reviews in Food Science and Nutrition, 43, 89-143. doi:10.1080/10408690390826464
[26] Nijveldt, R.J., Van Nood, E., Van Hoorn, D.E., Boelens, P.G., Van Norren, K. and Van Leeuwen, P.A. (2001) Flavonoids: A review of probable mechanisms of action and potential applications. American Journal of Clinical Nutrition, 74, 418-425.
[27] Fotsis, T., Pepper, M.S., Aktas, E., Breit, S., Rasku, S., Adlercreutz, H., Wahala, K., Montesano, R. and Schweigerer, L. (1997) Flavonoids, dietary-derived inhibittors of cell proliferation and in vitro angiogenesis. Cancer Research, 57, 2916-2921.
[28] Ramos, S. (2007) Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. Journal of Nutritional Biochem, 18, 427-442. doi:10.1016/j.jnutbio.2006.11.004
[29] Meeran, S.M., Patel, S.N., Chan, T.H. and Tollefsbol, T.O. (2011) A novel prodrug of epigallocatechin-3-gallate: Differential epigenetic hTERT repression in human breast cancer cells. Cancer Prevention Research (Phila), 4, 1243-1254. doi:10.1158/1940-6207.CAPR-11-0009
[30] Haghiac, M. and Walle, T. (2005) Quercetin induces necrosis and apoptosis in SCC-9 oral cancer cells. Nutrition and Cancer, 53, 220-231. doi:10.1207/s15327914nc5302_11
[31] Cheng, S., Gao, N., Zhang, Z., Chen, G., Budhraja, A., Ke, Z., Son, Y.O., Wang, X., Luo, J. and Shi, X. (2010) Quercetin induces tumor-selective apoptosis through downregulation of Mcl-1 and activation of Bax. Clinical Cancer Research, 16, 5679-5691. doi:10.1158/1078-0432.CCR-10-1565
[32] Chou, C.C., Yang, J.S., Lu, H.F., Ip, S.W., Lo, C., Wu, C.C., Lin, J.P., Tang, N.Y., Chung, J.G., Chou, M.J., Teng, Y.H. and Chen, D.R. (2010) Quercetin-mediated cell cycle arrest and apoptosis involving activation of a caspase cascade through the mitochondrial pathway in human breast cancer MCF-7 cells. Archives of Pharmacal Research, 33, 1181-1191. doi:10.1007/s12272-010-0808-y
[33] Nguyen, T.T., Tran, E., Nguyen, T.H., Do, P.T., Huynh, T.H. and Huynh, H. (2004) The role of activated MEK-ERK pathway in quercetin-induced growth inhibition and apoptosis in A549 lung cancer cells. Carcinogenesis, 25, 647-659. doi:10.1093/carcin/bgh052
[34] Senthilkumar, K., Elumalai, P., Arunkumar, R., Banudevi, S., Gunadharini, N.D., Sharmila, G., Selvakumar, K. and Arunakaran, J. (2010) Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3). Molecular and Cellular Biochemistry, 344, 173-184. doi:10.1007/s11010-010-0540-4
[35] van Erk, M.J., Roepman, P., van der Lende, T.R., Stierum, R.H., Aarts, J.M., van Bladeren, P.J. and Van Ommen, B. (2005) Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. European Journal of Nutrition, 44, 143-156. doi:10.1007/s00394-004-0503-1
[36] Mouria, M., Gukovskaya, A.S., Jung, Y., Buechler, P., Hines, O.J., Reber, H.A. and Pandol, S.J. (2002) Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis. International Journal of Cancer, 98, 761-769. doi:10.1002/ijc.10202
[37] Ramos, S., Alia, M., Bravo, L. and Goya, L. (2005) Comparative effects of food-derived polyphenols on the viability and apoptosis of a human hepatoma cell line (HepG2). Journal of Agricultural and Food Chemistry, 53, 1271-1280. doi:10.1021/jf0490798
[38] Galati, G., Teng, S., Moridani, M.Y., Chan, T.S. and O’Brien, P.J. (2000) Cancer chemoprevention and apoptosis mechanisms induced by dietary polyphenolics. Drug Metabolism and Drug Interactions, 17, 311-349. doi:10.1515/DMDI.2000.17.1-4.311
[39] Giovannini, C., Scazzocchio, B., Vari, R., Santangelo, C., D’Archivio, M. and Masella, R. (2007) Apoptosis in cancer and atherosclerosis: Polyphenol activities. Annali dell’Istituto Superiore di Sanita, 43, 406-416.
[40] Sarkar, F.H. and Li, Y. (2006) Using chemopreventive agents to enhance the efficacy of cancer therapy. Cancer Research, 66, 3347-3350. doi:10.1158/0008-5472.CAN-05-4526
[41] Chan, M.M., Fong, D., Soprano, K.J., Holmes, W.F. and Heverling, H. (2003) Inhibition of growth and sensitization to cisplatin-mediated killing of ovarian cancer cells by polyphenolic chemopreventive agents. Journal of Cellular Physiology, 194, 63-70. doi:10.1002/jcp.10186
[42] Khafif, A., Schantz, S.P., Chou, T.C., Edelstein, D. and Sacks, P.G. (1998) Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalignant and malignant human oral epithetlial cells. Carcinogenesis, 19, 419-424. doi:10.1093/carcin/19.3.419
[43] Sharma, H., Sen, S. and Singh, N. (2005) Molecular pathways in the chemosensitization of cisplatin by quercetin in human head and neck cancer. Cancer Biology and Therapy, 4, 949-955. doi:10.4161/cbt.4.9.1908
[44] Jakubowicz-Gil, J., Paduch, R., Piersiak, T., Glowniak, K., Gawron, A. and Kandefer-Szerszen, M. (2005) The effect of quercetin on pro-apoptotic activity of cisplatin in HeLa cells. Biochemical Pharmacology, 69, 1343-1350. doi:10.1016/j.bcp.2005.01.022
[45] Suganuma, M., Okabe, S., Kai, Y., Sueoka, N., Sueoka, E., Fujiki, H. (1999) Synergistic effects of (--)-epigallocatechin gallate with (--)-epicatechin, sulindac, or tamoxifen on cancer-preventive activity in the human lung cancer cell line PC-9. Cancer Research, 59, 44-47.
[46] Hwang, J.T., Ha, J. and Park, O.J. (2005) Combination of 5-fluorouracil and genistein induces apoptosis synergistically in chemo-resistant cancer cells through the modulation of AMPK and COX-2 signaling pathways. Biochemical and Biophysical Research Communications, 332, 433-440. doi:10.1016/j.bbrc.2005.04.143
[47] Passi, S., Picardo, M. and Nazzaro-Porro, M. (1987) Comparative cytotoxicity of phenols in vitro. Biochemical Journal, 245, 537-542.
[48] Moridani, M.Y., Galati, G. and O’Brien, P.J. (2002) Comparative quantitative structure toxicity relationships for flavonoids evaluated in isolated rat hepatocytes and HeLa tumor cells. Chemico-Biological Interactions, 139, 251-264. doi:10.1016/S0009-2797(02)00005-4
[49] Siraki, A.G., Chan, T.S. and O’Brien, P.J. (2004) Application of quantitative structure-toxicity relationships for the comparison of the cytotoxicity of 14 p-benzoquinone congeners in primary cultured rat hepatocytes versus PC12 cells. Toxicological Sciences, 81, 148-159. doi:10.1093/toxsci/kfh182
[50] Depeint, F., Gee, J.M., Williamson, G. and Johnson, I.T. (2002) Evidence for consistent patterns between flavonoid structures and cellular activities. Proceedings of the Nutrition Society, 61, 97-103. doi:10.1079/PNS2001133
[51] Gomes, C.A., da Cruz, T.G., Andrade, J.L., Milhazes, N., Borges, F. and Marques, M.P. (2003) Anticancer activity of phenolic acids of natural or synthetic origin: A structureactivity study. Journal of Medical Chemistry, 46, 5395-5401. doi:10.1021/jm030956v
[52] Teixeira, S., Siquet, C., Alves, C., Boal, I., Marques, M.P., Borges, F., Lima, J.L. and Reis, S. (2005) Structureproperty studies on the antioxidant activity of flavonoids present in diet. Free Radical Biology and Medicine, 39, 1099-1108. doi:10.1016/j.freeradbiomed.2005.05.028
[53] Kerr, J.F., Wyllie, A.H. and Currie, A.R. (1972) Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. British Journal of Cancer, 26, 239-257. doi:10.1038/bjc.1972.33
[54] Kurosaka, K., Takahashi, M., Watanabe, N. and Kobayashi, Y. (2003) Silent cleanup of very early apoptotic cells by macrophages. Journal of Immunology, 171, 4672-4679.
[55] Elmore, S. (2007) Apoptosis: A review of programmed cell death. Toxicologic Pathology, 35, 495-516. doi:10.1080/01926230701320337
[56] Denault, J.B. and Salvesen, G.S. (2002) Caspases: Keys in the ignition of cell death. Chemical Reviews, 102, 4489-4500. doi:10.1021/cr010183n
[57] Wang, Z.B., Liu, Y.Q. and Cui, Y.F. (2005) Pathways to caspase activation. Cell Biology International, 29, 489-496. doi:10.1016/j.cellbi.2005.04.001
[58] Rai, N.K., Tripathi, K., Sharma, D. and Shukla, V.K. (2005) Apoptosis: A basic physiologic process in wound healing. International Journal of Lower Extremity Wounds, 4, 138-144. doi:10.1177/1534734605280018
[59] Ziegler, D.S. and Kung, A.L. (2008) Therapeutic targeting of apoptosis pathways in cancer. Current Opinion in Oncology, 20, 97-103. doi:10.1097/CCO.0b013e3282f310f6
[60] Bucur, O., Ray, S., Bucur, M.C. and Almasan, A. (2006) APO2 ligand/tumor necrosis factor-related apoptosis-inducing ligand in prostate cancer therapy. Frontiers in Bioscience, 11, 1549-1568. doi:10.2741/1903
[61] Xiang, H., Nguyen, C.B., Kelley, S.K., Dybdal, N. and Escandon, E. (2004) Tissue distribution, stability, and pharmacokinetics of Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand in human colon carcinoma COLO205 tumor-bearing nude mice. Drug Metabolism and Disposition, 32, 1230-1238. doi:10.1124/dmd.104.000323
[62] Wang, J., Chun, H.J., Wong, W., Spencer, D.M. and Lenardo, M.J. (2001) Caspase-10 is an initiator caspase in death receptor signaling. Proceedings of the National Academy of Science of the Uited States of America, 98, 13884-13888. doi:10.1073/pnas.241358198
[63] Ghobrial, I.M., Witzig, T.E. and Adjei, A.A. (2005) Targeting apoptosis pathways in cancer therapy. CA—A Cancer Journal for Clinicians, 55, 178-194. doi:10.3322/canjclin.55.3.178
[64] Maldonado, V., Melendez-Zajgla, J. and Ortega, A. (1997) Modulation of NF-kappa B, and Bcl-2 in apoptosis induced by cisplatin in HeLa cells. Mutation Research, 381, 67-75. doi:10.1016/S0027-5107(97)00150-4
[65] Chen, L.F. and Greene, W.C. (2004) Shaping the nuclear action of NF-kappaB. Nature Reviews Molecular Cell Biology, 5, 392-401. doi:10.1038/nrm1368
[66] Stoffel, A., Chaurushiya, M., Singh, B. and Levine, A.J. (2004) Activation of NF-kappaB and inhibition of p53-mediated apoptosis by API2/mucosa-associated lymphoid tissue 1 fusions promote oncogenesis. Proceedings of the National Academy of Science of the Uited States of America, 101, 9079-9084. doi:10.1073/pnas.0402415101
[67] Kuhnel, F., Zender, L., Paul, Y., Tietze, M.K., Trautwein, C., Manns, M. and Kubicka, S. (2000) NFkappaB mediates apoptosis through transcriptional activation of Fas (CD95) in adenoviral hepatitis. Journal of Biological Chemistry, 275, 6421-6427. doi:10.1074/jbc.275.9.6421
[68] Cantley, L.C. (2002) The phosphoinositide 3-kinase pathway. Science, 296, 1655-1657. doi:10.1126/science.296.5573.1655
[69] Vanhaesebroeck, B., Leevers, S.J., Ahmadi, K., Timms, J., Katso, R., Driscoll, P.C., Woscholski, R., Parker, P.J. and Waterfield, M.D. (2001) Synthesis and function of 3-phosphorylated inositol lipids. Annual Review of Biochemistry, 70, 535-602. doi:10.1146/annurev.biochem.70.1.535
[70] Datta, S.R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y. and Greenberg, M.E. (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell, 91, 231-241. doi:10.1016/S0092-8674(00)80405-5
[71] del Peso, L., Gonzalez-Garcia, M., Page, C., Herrera, R. and Nunez, G. (1997) Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science, 278, 687-689. doi:10.1126/science.278.5338.687
[72] Barkett, M. and Gilmore, T.D. (1999) Control of apoptosis by Rel/NF-kappaB transcription factors. Oncogene, 18, 6910-6924. doi:10.1038/sj.onc.1203238
[73] Lauder, A., Castellanos, A. and Weston, K. (2001) c-Myb transcription is activated by protein kinase B (PKB) following interleukin 2 stimulation of Tcells and is required for PKB-mediated protection from apoptosis. Molecular and Cellular Biology, 21, 5797-5805. doi:10.1128/MCB.21.17.5797-5805.2001
[74] Fresno Vara, J.A., Casado, E., de Castro, J., Cejas, P., Belda-Iniesta, C. and Gonzalez-Baron, M. (2004) PI3K/ Akt signalling pathway and cancer. Cancer Treatment Reviews, 30, 193-204. doi:10.1016/j.ctrv.2003.07.007
[75] Saikumar, P., Dong, Z., Mikhailov, V., Denton, M., Weinberg, J.M. and Venkatachalam, M.A. (1999) Apoptosis: Definition, mechanisms, and relevance to disease. American Journal of Medicine, 107, 489-506. doi:10.1016/S0002-9343(99)00259-4
[76] Wyllie, A.H., Bellamy, C.O., Bubb, V.J., Clarke, A.R., Corbet, S., Curtis, L., Harrison, D.J., Hooper, M.L., Toft, N., Webb, S. and Bird, C.C. (1999) Apoptosis and carcinogenesis. British Journal of Cancer, 80, 34-37.
[77] Reed, J.C. (1999) Dysregulation of apoptosis in cancer. Journal of Clinical Oncology, 17, 2941-2953.
[78] Zhivotovsky, B. and Orrenius, S. (2006) Carcinogenesis and apoptosis: Paradigms and paradoxes. Carcinogenesis, 27, 1939-1945. doi:10.1093/carcin/bgl035
[79] Thompson, C.B. (1995) Apoptosis in the pathogenesis and treatment of disease. Science, 267, 1456-1462. doi:10.1126/science.7878464
[80] Hanahan, D. and Weinberg, R.A. (2000) The hallmarks of cancer. Cell, 100, 57-70. doi:10.1016/S0092-8674(00)81683-9
[81] Hueber, A.O. and Evan, G.I. (1998) Traps to catch unwary oncogenes. Trends in Genetics, 14, 364-367. doi:10.1016/S0168-9525(98)01520-0
[82] Harris, A.L. (2002) Hypoxia—A key regulatory factor in tumour growth. Nature Reviews Cancer, 2, 38-47. doi:10.1038/nrc704
[83] Wright, S.C., Zhong, J. and Larrick, J.W. (1994) Inhibition of apoptosis as a mechanism of tumor promotion. FASEB Journal, 8, 654-660.
[84] Roth, W. and Reed, J.C. (2002) Apoptosis and cancer: When BAX is TRAILing away. Nature Medicine, 8, 216218. doi:10.1038/nm0302-216
[85] Miyashita, T., Krajewski, S., Krajewska, M., Wang, H.G., Lin, H.K., Liebermann, D.A., Hoffman, B. and Reed, J.C. (1994) Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene, 9, 1799-1805.
[86] Wang, X.W. (1999) Role of p53 and apoptosis in carcinogenesis. Anticancer Research, 19, 4759-4771.
[87] Bourdon, J.C. (2007) p53 and its isoforms in cancer. British Journal of Cancer, 97, 277-282. doi:10.1038/sj.bjc.6603886
[88] Key, T.J., Schatzkin, A., Willett, W.C., Allen, N.E., Spencer, E.A. and Travis, R.C. (2004) Diet, nutrition and the prevention of cancer. Public Health Nutrition, 7, 187-200. doi:10.1079/PHN2003588
[89] Gonzalez, C.A. (2006) Nutrition and cancer: The current epidemiological evidence. British Journal of Nutrition, 96, S42-45. doi:10.1079/BJN20061699
[90] Sporn, M.B., Dunlop, N.M., Newton, D.L. and Smith, J.M. (1976) Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Federation Proceedings, 35, 1332-1338.
[91] Bouchier-Hayes, L., Lartigue, L. and Newmeyer, D.D. (2005) Mitochondria: pharmacological manipulation of cell death. Journal of Clinical Investigation, 115, 2640-2647. doi:10.1172/JCI26274
[92] Kelloff, G.J., Sigman, C.C. and Greenwald, P. (1999) Cancer chemoprevention: Progress and promise. European Journal of Cancer, 35, 2031-2038. doi:10.1016/S0959-8049(99)00299-3
[93] Kakizoe, T. (2003) Chemoprevention of cancer—Focusing on clinical trials. Japanese Journal of Clinical Oncology, 33, 421-442. doi:10.1093/jjco/hyg090
[94] Luqman, S. and Pezzuto, J.M. (2010) NFkappaB: A promising target for natural products in cancer chemo-prevention. Phytotherapy Research: PTR, 24, 949-963.
[95] Karin, M. (2006) Nuclear factor-kappaB in cancer development and progression. Nature, 441, 431-436. doi:10.1038/nature04870
[96] Crowell, J.A., Steele, V.E. and Fay, J.R. (2007) Targeting the AKT protein kinase for cancer chemoprevention. Molecular Cancer Therapeutics, 6, 2139-2148. doi:10.1158/1535-7163.MCT-07-0120
[97] Yang, C.S., Maliakal, P. and Meng, X. (2002) Inhibition of carcinogenesis by tea. Annual Review of Pharmacology and Toxicology, 42, 25-54. doi:10.1146/annurev.pharmtox.42.082101.154309
[98] Ahmad, N., Feyes, D.K., Nieminen, A.L., Agarwal, R. and Mukhtar, H. (1997) Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells. Journl of the National Cancer Institute, 89, 1881-1886. doi:10.1093/jnci/89.24.1881
[99] Albrecht, D.S., Clubbs, E.A., Ferruzzi, M. and Bomser, J.A. (2008) Epigallocatechin-3-gallate (EGCG) inhibits PC-3 prostate cancer cell proliferation via MEK-independent ERK1/2 activation. Chemico-Biological Interactions, 171, 89-95. doi:10.1016/j.cbi.2007.09.001
[100] Butt, M.S. and Sultan, M.T. (2009) Green tea: Nature’s defense against malignancies. Critical Reviews in Food Science and Nutrition, 49, 463-473. doi:10.1080/10408390802145310
[101] Khan, N. and Mukhtar, H. (2008) Multitargeted therapy of cancer by green tea polyphenols. Cancer Letters, 269, 269-280. doi:10.1016/j.canlet.2008.04.014
[102] Shimizu, M., Shirakami, Y. and Moriwaki, H. (2008) Targeting receptor tyrosine kinases for chemoprevention by green tea catechin, EGCG. International Journal of Molecular Sciences, 9, 1034-1049. doi:10.3390/ijms9061034
[103] Hastak, K., Gupta, S., Ahmad, N., Agarwal, M.K., Agarwal, M.L. and Mukhtar, H. (2003) Role of p53 and NF-kappaB in epigallocatechin-3-gallate-induced apoptosis of LNCaP cells. Oncogene, 22, 4851-4859. doi:10.1038/sj.onc.1206708
[104] Chung, L.Y., Cheung, T.C., Kong, S.K., Fung, K.P., Choy, Y.M., Chan, Z.Y. and Kwok, T.T. (2001) Induction of apoptosis by green tea catechins in human prostate cancer DU145 cells. Life Sciences, 68, 1207-1214. doi:10.1016/S0024-3205(00)01020-1
[105] Ahmad, N., Gupta, S. and Mukhtar, H. (2000) Green tea polyphenol epigallocatechin-3-gallate differentially modulates nuclear factor kappaB in cancer cells versus normal cells. Archives of Biochemistry and Biophys, 376, 338-346. doi:10.1006/abbi.2000.1742
[106] Afaq, F., Adhami, V.M., Ahmad, N. and Mukhtar, H. (2003) Inhibition of ultraviolet B-mediated activation of nuclear factor κB in normal human epidermal keratinocytes by green tea Constituent (-)-epigallocatechin-3-gallate. Oncogene, 22, 1035-1044. doi:10.1038/sj.onc.1206206
[107] Suganuma, M., Sueoka, E., Sueoka, N., Okabe, S. and Fujiki, H. (2000) Mechanisms of cancer prevention by tea polyphenols based on inhibition of TNF-alpha expression. Biofactors, 13, 67-72. doi:10.1002/biof.5520130112
[108] Qin, J., Xie, L.P., Zheng, X.Y., Wang, Y.B., Bai, Y., Shen, H.F., Li, L.C. and Dahiya, R. (2007) A component of green tea, (-)-epigallocatechin-3-gallate, promotes apoptosis in T24 human bladder cancer cells via modulation of the PI3K/Akt pathway and Bcl-2 family proteins. Biochemical and Biophysical Research Communications, 354, 852-857. doi:10.1016/j.bbrc.2007.01.003
[109] Rodriguez, S.K., Guo, W., Liu, L., Band, M.A., Paulson, E.K. and Meydani, M. (2006) Green tea catechin, epigallocatechin-3-gallate, inhibits vascular endothelial growth factor angiogenic signaling by disrupting the formation of a receptor complex. International Journal of Cancer, 118, 1635-1644. doi:10.1002/ijc.21545
[110] Tang, F.Y., Nguyen, N. and Meydani, M. (2003) Green tea catechins inhibit VEGF-induced angiogenesis in vitro through suppression of VE-cadherin phosphorylation and inactivation of Akt molecule. International Journal of Cancer, 106, 871-878. doi:10.1002/ijc.11325
[111] Masuda, M., Suzui, M., Lim, J.T., Deguchi, A., Soh, J.W. and Weinstein, I.B. (2002) Epigallocatechin-3-gallate decreases VEGF production in head and neck and breast carcinoma cells by inhibiting EGFR-related pathways of signal transduction. Journal of Experimental Therapeutics and Oncology, 2, 350-359. doi:10.1046/j.1359-4117.2002.01062.x
[112] Gupta, S., Hussain, T. and Mukhtar, H. (2003) Molecular pathway for (-)-epigallocatechin-3-gallate-induced cell cycle arrest and apoptosis of human prostate carcinoma cells. Archives of Biochemistry and Biophysics, 410, 177-185. doi:10.1016/S0003-9861(02)00668-9
[113] Shankar, S., Suthakar, G. and Srivastava, R.K. (2007) Epigallocatechin-3-gallate inhibits cell cycle and induces apoptosis in pancreatic cancer. Frontiers in Bioscience, 12, 5039-5051. doi:10.2741/2446
[114] Kuo, P.L., Lin, C.C. (2003) Green tea constituent (-)-epigallocatechin-3-gallate inhibits Hep G2 cell proliferation and induces apoptosis through p53-dependent and Fasmediated pathways. Journal of Biomedical Science, 10, 219-227.
[115] Ju, J., Hong, J., Zhou, J.N., Pan, Z., Bose, M., Liao, J., Yang, G.Y., Liu, Y.Y., Hou, Z., Lin, Y., Ma, J., Shih, W.J., Carothers, A.M. and Yang, C.S. (2005) Inhibition of intestinal tumorigenesis in Apcmin/+ mice by (-)-epigallocatechin-3-gallate, the major catechin in green tea. Cancer Research, 65, 10623-10631. doi:10.1158/0008-5472.CAN-05-1949
[116] Shimizu, M., Shirakami, Y., Sakai, H., Adachi, S., Hata, K., Hirose, Y., Tsurumi, H., Tanaka, T. and Moriwaki, H. (2008) (-)-Epigallocatechin gallate suppresses azoxymethane-induced colonic premalignant lesions in male C57BL/KsJdb/db mice. Cancer Prevention Research (Phila), 1, 298-304. doi:10.1158/1940-6207.CAPR-08-0045
[117] Shimizu, M., Sakai, H., Shirakami, Y., Yasuda, Y., Kubota, M., Terakura, D., Baba, A., Ohno, T., Hara, Y., Tanaka, T. and Moriwaki, H. (2011) Preventive effects of (-)-epigallocatechin gallate on diethylnitrosamine-induced liver tumorigenesis in obese and diabetic C57BL/KsJ-db/db Mice. Cancer Prevention Research (Phila), 4, 396-403. doi:10.1158/1940-6207.CAPR-10-0331
[118] Ohga, N., Hida, K., Hida, Y., Muraki, C., Tsuchiya, K., Matsuda, K., Ohiro, Y., Totsuka, Y. and Shindoh, M. (2009) Inhibitory effects of epigallocatechin-3 gallate, a polyphenol in green tea, on tumor-associated endothelial cells and endothelial progenitor cells. Cancer Science, 100, 1963-1970. doi:10.1111/j.1349-7006.2009.01255.x
[119] Rieger-Christ, K.M., Hanley, R., Lodowsky, C., Bernier, T., Vemulapalli, P., Roth, M., Kim, J., Yee, A.S., Le, S.M., Marie, P.J., Libertino, J.A. and Summerhayes, I.C. (2007) The green tea compound, (-)-epigallocatechin-3-gallate downregulates N-cadherin and suppresses migration of bladder carcinoma cells. Journal of Cellular Biochemistry, 102, 377-388. doi:10.1002/jcb.21299
[120] Aggarwal, B.B., Kumar, A. and Bharti, A.C. (2003) Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Research, 23, 363-398.
[121] Bharti, A.C., Donato, N., Singh, S. and Aggarwal, B.B. (2003) Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood, 101, 1053-1062. doi:10.1182/blood-2002-05-1320
[122] Hussain, A.R., Ahmed, M., Al-Jomah, N.A., Khan, A.S., Manogaran, P., Sultana, M., Abubaker, J., Platanias, L.C., Al-Kuraya, K.S. and Uddin, S. (2008) Curcumin suppresses constitutive activation of nuclear factor-kappa B and requires functional Bax to induce apoptosis in Burkitt’s lymphoma cell lines. Molecular Cancer Therapeutics, 7, 3318-3329. doi:10.1158/1535-7163.MCT-08-0541
[123] Kunnumakkara, A.B., Diagaradjane, P., Guha, S., Deorukhkar, A., Shentu, S., Aggarwal, B.B. and Krishnan, S. (2008) Curcumin sensitizes human colorectal cancer xenografts in nude mice to gamma-radiation by targeting nuclear factor-kappaB-regulated gene products. Clinical Cancer Research, 14, 2128-2136. doi:10.1158/1078-0432.CCR-07-4722
[124] Wang, D., Veena, M.S., Stevenson, K., Tang, C., Ho, B., Suh, J.D., Duarte, V.M., Faull, K.F., Mehta, K., Srivatsan, E.S. and Wang, M.B. (2008) Liposome-encapsulated curcumin suppresses growth of head and neck squamous cell carcinoma in vitro and in xenografts through the inhibittion of nuclear factor kappaB by an AKT-independent pathway. Clinical Cancer Research, 14, 6228-6236. doi:10.1158/1078-0432.CCR-07-5177
[125] Al-Hujaily, E.M., Mohamed, A.G., Al-Sharif, I., Youssef, K.M., Manogaran, P.S., Al-Otaibi, B., Al-Haza’a, A., Al-Jammaz, I., Al-Hussein, K. and Aboussekhra, A. (2011) PAC, a novel curcumin analogue, has anti-breast cancer properties with higher efficiency on ER-negative cells. Breast Cancer Research and Treatment, 128, 97-107. doi:10.1007/s10549-010-1089-3
[126] Dhillon, N., Aggarwal, B.B., Newman, R.A., Wolff, R.A., Kunnumakkara, A.B., Abbruzzese, J.L., Ng, C.S., Badmaev, V. and Kurzrock, R. (2008) Phase II trial of curcumin in patients with advanced pancreatic cancer. Clinical Cancer Research, 14, 4491-4499. doi:10.1158/1078-0432.CCR-08-0024
[127] Yu, S., Shen, G., Khor, T.O., Kim, J.H. and Kong, A.N. (2008) Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase-dependent mechanism. Molecular Cancer Therapeutics, 7, 2609-2620. doi:10.1158/1535-7163.MCT-07-2400
[128] Clark, C.A., McEachern, M.D., Shah, S.H., Rong, Y., Rong, X., Smelley, C.L., Caldito, G.C., Abreo, F.W. and Nathan, C.O. (2010) Curcumin inhibits carcinogen and nicotine-induced Mammalian target of rapamycin pathway activation in head and neck squamous cell carcinoma. Cancer Prevention Research (Phila), 3, 1586-1595. doi:10.1158/1940-6207.CAPR-09-0244
[129] Weir, N.M., Selvendiran, K., Kutala, V.K., Tong, L., Vishwanath, S., Rajaram, M., Tridandapani, S., Anant, S. and Kuppusamy, P. (2007) Curcumin induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by modulating Akt and p38 MAPK. Cancer Biology and Therapy, 6, 178-184. doi:10.4161/cbt.6.2.3577
[130] Kumar, A.P., Garcia, G.E., Ghosh, R., Rajnarayanan, R.V., Alworth, W.L. and Slaga, T.J. (2003) 4-Hydroxy-3-methoxy-benzoic acid methyl ester: A curcumin derivative targets Akt/NF kappa B cell survival signaling pathway: Potential for prostate cancer management. Neoplasia, 5, 255-266.
[131] Squires, M.S., Hudson, E.A., Howells, L., Sale, S., Houghton, C.E., Jones, J.L., Fox, L.H., Dickens, M., Prigent, S.A. and Manson, M.M. (2003) Relevance of mitogen activated protein kinase (MAPK) and phosphotidy-linositol-3-kinase/protein kinase B (PI3K/PKB) pathways to induction of apoptosis by curcumin in breast cells. Biochemical Pharmacology, 65, 361-376. doi:10.1016/S0006-2952(02)01517-4
[132] Woo, J.H., Kim, Y.H., Choi, Y.J., Kim, D.G., Lee, K.S., Bae, J.H., Min, D.S., Chang, J.S., Jeong, Y.J., Lee, Y.H., Park, J.W. and Kwon, T.K. (2003) Molecular mechanisms of curcumin-induced cytotoxicity: Induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-XL and IAP, the release of cytochrome c and inhibition of Akt. Carcinogenesis, 24, 1199-1208. doi:10.1093/carcin/bgg082
[133] Subramaniam, D., May, R., Sureban, S.M., Lee, K.B., George, R., Kuppusamy, P., Ramanujam, R.P., Hideg, K., Dieckgraefe, B.K., Houchen, C.W. and Anant, S. (2008) Diphenyl difluoroketone: A curcumin derivative with potent in vivo anticancer activity. Cancer Research, 68, 1962-1969. doi:10.1158/0008-5472.CAN-07-6011
[134] Purkayastha, S., Berliner, A., Fernando, S.S., Ranasinghe, B., Ray, I., Tariq, H. and Banerjee, P. (2009) Curcumin Blocks Brain Tumor Formation. Brain Research, 1266, 130-138. doi:10.1016/j.brainres.2009.01.066
[135] Deschner, E.E., Ruperto, J., Wong, G. and Newmark, H.L. (1991) Quercetin and rutin as inhibitors of azoxymethanolinduced colonic neoplasia. Carcinogenesis, 12, 1193-1196. doi:10.1093/carcin/12.7.1193
[136] De, S., Chakraborty, R.N., Ghosh, S., Sengupta and A., Das, S. (2004) Comparative evaluation of cancer chemopreventive efficacy of alpha-tocopherol and quercetin in a murine model. Journal of Experimental and Clinical Cancer Research, 23, 251-258.
[137] Volate, S.R., Davenport, D.M., Muga, S.J. and Wargovich, M.J. (2005) Modulation of aberrant crypt foci and apoptosis by dietary herbal supplements (quercetin, curcumin, silymarin, ginseng and rutin). Carcinogenesis, 26, 1450-1456. doi:10.1093/carcin/bgi089
[138] Cruz-Correa, M., Shoskes, D.A., Sanchez, P., Zhao, R., Hylind, L.M., Wexner, S.D. and Giardiello, F.M. (2006) Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clinical Gastroenterology and Hepatology, 4, 1035-1038. doi:10.1016/j.cgh.2006.03.020
[139] Kawanishi, S., Oikawa, S. and Murata, M. (2005) Evaluation for safety of antioxidant chemopreventive agents. Antioxidants and Redox Signaling, 7, 1728-1739. doi:10.1089/ars.2005.7.1728
[140] Kim, B.M., Choi, Y.J., Han, Y., Yun, Y.S. and Hong, S.H. (2009) N,N-dimethyl phytosphingosine induces caspase-8dependent cytochrome c release and apoptosis through ROS generation in human leukemia cells. Toxicology and Applied Pharmacology, 239, 87-97. doi:10.1016/j.taap.2009.05.020
[141] Jung, Y.H., Heo, J., Lee, Y.J., Kwon, T.K. and Kim, Y.H. (2010) Quercetin enhances TRAIL-induced apoptosis in prostate cancer cells via increased protein stability of death receptor 5. Life Sciences, 86, 351-357. doi:10.1016/j.lfs.2010.01.008
[142] Lee, D.H., Szczepanski, M. and Lee, Y.J. (2008) Role of Bax in quercetin-induced apoptosis in human prostate cancer cells. Biochemical Pharmacology, 75, 2345-2355. doi:10.1016/j.bcp.2008.03.013
[143] Senthilkumar, K., Elumalai, P., Arunkumar, R., Banudevi, S., Gunadharini, N.D., Sharmila, G., Selvakumar, K. and Arunakaran, J. (2010) Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3). Molecular and Cellular Biochemistry, 344, 173-184. doi:10.1007/s11010-010-0540-4
[144] Kim, Y.H. and Lee, Y.J. (2007) TRAIL apoptosis is enhanced by quercetin through Akt dephosphorylation. Journal of Cellular Biochemistry, 100, 998-1009. doi:10.1002/jcb.21098
[145] Russo, M., Palumbo, R., Tedesco, I., Mazzarella, G., Russo, P., Iacomino, G., Russo, G.L. (1999) Quercetin and anti-CD95(Fas/Apo1) enhance apoptosis in HPB-ALL cell line. FEBS Letters, 462, 322-328. doi:10.1016/S0014-5793(99)01544-6
[146] Ishikawa, Y. and Kitamura, M. (2000) Anti-apoptotic effect of quercetin: Intervention in the JNKand ERK-mediated apoptotic pathways. Kidney International, 58, 1078-1087. doi:10.1046/j.1523-1755.2000.00265.x
[147] Sun, Z.J., Chen, G., Hu, X., Zhang, W., Liu, Y., Zhu, L.X., Zhou, Q. and Zhao, Y.F. (2010) Activation of PI3K/Akt/ IKK-alpha/NF-kappaB signaling pathway is required for the apoptosis-evasion in human salivary adenoid cystic carcinoma: its inhibition by quercetin. Apoptosis: An International Journal on Programmed Cell Death, 15, 850-863.
[148] Scandlyn, M.J., Stuart, E.C., Somers-Edgar, T.J., Menzies, A.R. and Rosengren, R.J. (2008) A new role for tamoxifen in oestrogen receptor-negative breast cancer when it is combined with epigallocatechin gallate. British Journal of Cancer, 99, 1056-1063. doi:10.1038/sj.bjc.6604634
[149] Sartippour, M.R., Pietras, R., Marquez-Garban, D.C., Chen, H.W., Heber, D., Henning, S.M., Sartippour, G., Zhang, L., Lu, M., Weinberg, O., Rao, J.Y. and Brooks, M.N. (2006) The combination of green tea and tamoxifen is effective against breast cancer. Carcinogenesis, 27, 2424-2433. doi:10.1093/carcin/bgl066
[150] Somers-Edgar, T.J., Scandlyn, M.J., Stuart, E.C., Le Nedelec, M.J., Valentine, S.P. and Rosengren, R.J. (2008) The combination of epigallocatechin gallate and curcumin suppresses ER alpha-breast cancer cell growth in vitro and in vivo. International Journal of Cancer, 122, 1966-1971. doi:10.1002/ijc.23328
[151] Kunnumakkara, A.B., Guha, S., Krishnan, S., Diagaradjane, P., Gelovani, J. and Aggarwal, B.B. (2007) Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Research, 67, 3853-3861. doi:10.1158/0008-5472.CAN-06-4257
[152] Bisht, S., Mizuma, M., Feldmann, G., Ottenhof, N.A., Hong, S.M., Pramanik, D., Chenna, V., Karikari, C., Sharma, R., Goggins, M.G., Rudek, M.A., Ravi and R., Maitra, A. (2010) Systemic administration of polymeric nanoparticle-encapsulated curcumin (NanoCurc) blocks tumor growth and metastases in preclinical models of pancreatic cancer. Molecular Cancer Therapeutics, 9, 2255-2264. doi:10.1158/1535-7163.MCT-10-0172
[153] Zhou, W., Kallifatidis, G., Baumann, B., Rausch, V., Mattern, J., Gladkich, J., Giese, N., Moldenhauer, G., Wirth, T., Buchler, M.W., Salnikov, A.V. and Herr, I. (2010) Dietary polyphenol quercetin targets pancreatic cancer stem cells. International Journal of Oncology, 37, 551-561.
[154] Narayanan, N.K., Nargi, D., Randolph, C. and Narayanan, B.A. (2009) Liposome encapsulation of curcumin and resveratrol in combination reduces prostate cancer incidence in PTEN knockout mice. International Journal of Cancer, 125, 1-8. doi:10.1002/ijc.24336
[155] Priego, S., Feddi, F., Ferrer, P., Mena, S., Benlloch, M., Ortega, A., Carretero, J., Obrador, E., Asensi, M. and Estrela, J.M. (2008) Natural polyphenols facilitate elimination of HT-29 colorectal cancer xenografts by chemoradiotherapy: a Bcl-2and superoxide dismutase 2-dependent mechanism. Molecular Cancer Therapeutics, 7, 3330-3342. doi:10.1158/1535-7163.MCT-08-0363
[156] Sreekanth, C.N., Bava, S.V., Sreekumar, E. and Anto, R.J. (2011) Molecular evidences for the chemosensitizing efficacy of liposomal curcumin in paclitaxel chemotherapy in mouse models of cervical cancer. Oncogene, 30, 3139-3152. doi:10.1038/onc.2011.23
[157] Duarte, V.M., Han, E., Veena, M.S., Salvado, A., Suh, J.D., Liang, L.J., Faull, K.F., Srivatsan, E.S. and Wang, M.B. (2010) Curcumin enhances the effect of cisplatin in suppression of head and neck squamous cell carcinoma via inhibition of IKKbeta protein of the NFkappaB pathway. Molecular Cancer Therapeutics, 9, 2665-2675. doi:10.1158/1535-7163.MCT-10-0064
[158] Nautiyal, J., Banerjee, S., Kanwar, S.S., Yu, Y., Patel, B.B., Sarkar, F.H. and Majumdar, A.P. (2011) Curcumin enhances dasatinib-induced inhibition of growth and transformation of colon cancer cells. International Journal of Cancer, 128, 951-961. doi:10.1002/ijc.25410
[159] Reed, J.C. (2001) Apoptosis-regulating proteins as targets for drug discovery. Trends in Molecular Medicine, 7, 314-319. doi:10.1016/S1471-4914(01)02026-3
[160] Willett, W.C. (1995) Diet, nutrition, and avoidable cancer. Environmental Health Perspectives, 103, 165-170.
[161] Howells, L.M. and Manson, M.M. (2005) Prospects for plant-derived chemopreventive agents exhibiting multiple mechanisms of action. Current Medicinal Chemistry—AntiCancer Agents, 5, 201-213. doi:10.2174/1568011053765921

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