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Cancer Chemoprevention by Natural Products: How Far Have We Come?

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ABSTRACT

Since ancient times, natural products, herbs and spices have been used for preventing several diseases, including cancer. The term chemoprevention was coined in the late 1970s and referred to the prevention of cancer by selective use of phytochemicals or their analogs. The field utilizes experimental carcinogenesis models to examine the efficacy of chemopreventive agents in a stage-specific manner. The concept of using naturally derived chemicals as potential chemopreventive agents has advanced the field dramatically. Throughout the years, a vast number of chemopreventive agents present in natural products have been evaluated using various experimental models. A number of them have progressed to early clinical trials. More recently, the focus has been directed towards molecular targeting of chemopreventive agents to identify mechanism(s) of action of these newly discovered bioactive compounds. Moreover, it has been recognized that single agents may not always be sufficient to provide chemopreventive efficacy, and, therefore, the new concept of combination chemoprevention by multiple agents or by the consumption of “whole foods” has become an increasingly attractive area of study. Novel technologies, such as nanotechnology, along with a better understanding of cancer stem cells, are certain to continue the advancement of the field of cancer chemoprevention in years to come.

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REFERENCES

  1. Karpozilos A, Pavlidis N. The treatment of cancer in Greek antiquity. Eur J Cancer. 2004;40:2033–40.

    Article  PubMed  CAS  Google Scholar 

  2. Rafter JJ. Scientific basis of biomarkers and benefits of functional foods for reduction of disease risk: Cancer. Br J Nutr. 2002;88:S219–24.

    Article  PubMed  CAS  Google Scholar 

  3. Colic M, Pavelic K. Molecular, cellular and medical aspects of the action of nutraceuticals and small molecules therapeutics: from chemoprevention to new drug development. Drugs Exp Clin Res. 2002;28:169–75.

    PubMed  CAS  Google Scholar 

  4. Murillo G, Mehta RG. Cruciferous vegetables and cancer prevention. Nutr Cancer. 2001;41:17–28.

    Article  PubMed  CAS  Google Scholar 

  5. Ambrosone CB, Tang L. Cruciferous vegetable intake and cancer prevention: role of nutrigenetics. Cancer Prev Res. 2009;2:298–300.

    Article  Google Scholar 

  6. Reuter S, Eifes S, Dicato M, Aggarwal BB, Diederich M. Modulation of anti-apoptotic and survival pathways by curcumin as a strategy to induce apoptosis in cancer cells. Biochem Pharmacol. 2008;76:1340–51.

    Article  PubMed  CAS  Google Scholar 

  7. Yang CS, Wang X, Lu G, Picinich SC. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat Rev Cancer. 2009;9:429–39.

    Article  PubMed  CAS  Google Scholar 

  8. Yu C, Shin YG, Chow A, Li Y, Kosmeder JW, Lee YS, et al. Human, rat, and mouse metabolism of resveratrol. Pharm Res. 2002;19:1907–14.

    Article  PubMed  CAS  Google Scholar 

  9. Garikapaty VP, Ashok BT, Mittelman TK, Tiwari RK. Synthetic dimmer of indole-3-carbinol: second generation diet derived anti-cancer agent in hormone sensitive prostate cancer. Prostate. 2006;66:453–62.

    Article  PubMed  CAS  Google Scholar 

  10. Ko KP, Park SK, Cho LY, Gwack J, Yang JJ, Shin A, et al. Soybean product intake modifies the association between interleukin-10 genetic polymorphisms and gastric cancer risk. J Nutr. 2009;139:1008–12.

    Article  PubMed  CAS  Google Scholar 

  11. Balachandran P, Govindrajan R. Cancer an Ayurvedic perspective. Pharmacol Res. 2005;51:19–30.

    PubMed  Google Scholar 

  12. Xutian S, Zhang J, Louise W. New exploration and understanding of traditional Chinese medicine. Am J Chin Med. 2009;37:411–26.

    Article  PubMed  Google Scholar 

  13. Kunow MA. Maya Medicine: traditional healing in Yucatan. New Mexico: University of New Mexico Press; 2003.

    Google Scholar 

  14. Mena-Rajon G, Caamal-Fuentes E, Cantillo-Ciau Z, Cedillo-Rivera R, Flores-Guido J, Moo-Puc R. In vitro cytotoxic activity of nine plants used in Mayan Traditional medicine. J Ethnopharmacol. 2009;121:462–5.

    Article  Google Scholar 

  15. Sporn MB, Dunlop NM, Newton DL, Smith JM. Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed Proc. 1976;35:1332–8.

    PubMed  CAS  Google Scholar 

  16. Wattenberg LW. Inhibition of carcinogenesis by minor a nutrient constituents of the diet. Proc Nutr Soc. 1990;49:173–83.

    Article  PubMed  CAS  Google Scholar 

  17. Naithani R, Huma L, Moriarty R, McCormick DL, Mehta RG. Comprehensive review of cancer chemopreventive agents evaluated in experimental chemoprevention models and clinical trials. Current Med Chem. 2008;15:1044–71.

    Article  CAS  Google Scholar 

  18. Kwon KH, Barve A, Yu S, Huang MT, Kong AN. Cancer chemoprevention by phytochemicals potential molecular targets biomarkers and animal studies. Acta Pharmacol Sin. 2007;28:1409–21.

    Article  PubMed  CAS  Google Scholar 

  19. Singh RP, Agarwal R. Prostate cancer chemoprevention by silibinin: bench to bedside. Mol Carcinog. 2006;45:436–42.

    Article  PubMed  CAS  Google Scholar 

  20. Abate-Shen C, Brown PH, Colburn NH, Gerner EW, Green JE, Lipkin M, et al. The untapped potential of genetically engineered mouse models in chemoprevention research opportunities and challenges. Cancer Prev Res. 2008;3:161–6.

    Article  Google Scholar 

  21. Guilford JM, Pezzuto JM. Natural products as inhibitors of carcinogenesis. Expert Opin Investig Drugs. 2008;17:1341–52.

    Article  PubMed  CAS  Google Scholar 

  22. Kinghorn AD, Su BN, Jang DS, Chang LC, Lee D, Gu JQ, et al. Natural inhibitors of carcinogenesis. Planta Med. 2004;70:691–705.

    Article  PubMed  CAS  Google Scholar 

  23. Kosmeder 2nd JW, Pezzuto JM. Novel plant derived anticarcinogens. IARC Sci Publ Rev. 2002;156:343–7.

    Google Scholar 

  24. Lippman SM, Hawk ET. Cancer prevention: from 1727 to milestones of the past 100 years. Cancer Res. 2009;69:5269–84.

    Article  PubMed  CAS  Google Scholar 

  25. Mehta RG, Hussain EA, Mehta RR, Das Gupta TK. Chemoprevention of mammary carcinogenesis by 1α-hydroxyvitamin D5 a synthetic analog of vitamin D. Mutation Res. 2003;523–524:253–64.

    PubMed  Google Scholar 

  26. Milner JA. Nutrition and cancer: essential elements for a roadmap. Cancer Lett. 2008;269:189–98.

    Article  PubMed  CAS  Google Scholar 

  27. Liu RJ, Dong HW, Chen BQ, Zhao P, Liu RH. Fresh apples suppress mammary carcinogenesis and proliferative activity and induce apoptosis in mammary tumors of the Sprague-Dawley rat. J Agric Food Chem. 2009;57:297–304.

    Article  PubMed  CAS  Google Scholar 

  28. Canene-Adams K, Lindshield BL, Wang S, Jeffery EH, Clinton SK, Erdman Jr JW. Combination of tomato and broccoli enhanced antitumor activity in Dunning R3227-H prostate adenocarcinomas. Cancer Res. 2007;67:836–43.

    Article  PubMed  CAS  Google Scholar 

  29. Thompson MD, Thompson HJ, Brick MA, McGinley JN, Jiang W, Zhu Z, et al. Mechanisms associated with dose-dependent inhibition of rat mammary carcinogenesis by dry bean (Phaseolus vulgaris, L.). J Nutr. 2008;138:2091–7.

    Article  PubMed  CAS  Google Scholar 

  30. Murillo G, Choi JK, Pan O, Hawthorne ME, Constantinou AI, Mehta RG. Garbanzo flour is as effective as soy flour at suppressing the formation of carcinogen-induced aberrant crypt foci in the colons of CF-1 mice. Anti-Cancer Res. 2004;24:3049–55.

    Google Scholar 

  31. Stoner GD. Foodstuffs for preventing cancer: the preclinical and clinical development of berries. Cancer Res. 2009;2:187–94.

    Google Scholar 

  32. Andreassen PR, Ho GP, D’Andrea AD. DNA damage responses and their many interactions with the replication fork. Carcinogenesis. 2006;27:883–92.

    Article  PubMed  CAS  Google Scholar 

  33. Khan N, Afaq F, Mukhtar H. Apoptosis by dietary factors: the suicide solution for delaying cancer growth. Carcinogenesis. 2007;28:233–9.

    Article  PubMed  CAS  Google Scholar 

  34. Lee JH, Lee HH, Lee HS, Choi JS, Kim KW, Hong SS. Deguelin inhibits human hepatocellular carcinoma by antiangiogenesis and apoptosis. Oncol Rep. 2008;20:129–34.

    PubMed  CAS  Google Scholar 

  35. Li Y, VandenBoom 2nd TG, Kong D, Wang Z, Ali S, Philip PA, et al. Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells. Cancer Res. 2009;69:6704–12.

    Article  PubMed  CAS  Google Scholar 

  36. Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, et al. Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet. 2005;37:766–70.

    Article  PubMed  CAS  Google Scholar 

  37. Ahmed FE. Role of miRNA in carcinogenesis and biomarker selection: a methodological view. Expert Rev Mol Diagn. 2007;7:569–603.

    Article  PubMed  CAS  Google Scholar 

  38. Lee YS, Dutta A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev. 2007;21:1025–30.

    Article  PubMed  CAS  Google Scholar 

  39. Davis CD, Ross SA. Evidence for dietary regulation of microRNA expression in cancer cells. Nutr Rev. 2008;66:477–82.

    Article  PubMed  Google Scholar 

  40. Marsit CJ, Eddy K, Kelsey KT. MicroRNA responses to cellular stress. Cancer Res. 2006;66:10843–8.

    Article  PubMed  CAS  Google Scholar 

  41. Garzon R, Pichiorri F, Palumbo T, Visentini M, Aqeilan R, Cimmino A, et al. MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia. Oncogene. 2007;26:4148–57.

    Article  PubMed  CAS  Google Scholar 

  42. Sun M, Estrov Z, Ji Y, Coombes KR, Harris DH, Kurzrock R. Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells. Mol Cancer Ther. 2008;7:464–73.

    Article  PubMed  CAS  Google Scholar 

  43. Sonkoly E, Wei T, Pavez Loriè E, Suzuki H, Kato M, Törmä H, et al. Protein kinase C-dependent upregulation of miR-203 induces the differentiation of human keratinocytes. J Invest Dermatol. 2009. doi:10.1038/jid.2009.294.

    Google Scholar 

  44. Melkamu T, Zhang X, Tan J, Zeng Y, Kassie F. Alteration of microRNA expression in vinyl-carbamate-induced mouse lung tumors and modulation by the chemopreventive agent indole-3-carbinol. Carcinogenesis. 2010;31:252–8.

    Google Scholar 

  45. Siddiqui IA, Adhami VM, Bharali DJ, Hafeez BB, Asim M, Khwaja SI, et al. Introducing nanochemoprevention as a novel approach for cancer control: proof of principle with green tea polyphenol epigallocatechin-3-gallate. Cancer Res. 2009;69:1712–6.

    Article  PubMed  CAS  Google Scholar 

  46. Teskac K, Kristi J. The evidence for solid lipid nanoparticles mediated cell uptake of resveratrol Int J Pharmacol. 2009; PMID 19833178.

  47. Murillo G, Peng X, Torres K, Mehta RG. Deguelin inhibits growth of breast cancer cells by modulating the expression of key members of the Wnt signaling pathway. Cancer Prev Res. 2009;2:942–50.

    Article  Google Scholar 

  48. Whyte L, Huang YY, Torres K, Mehta RG. Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses. Cancer Res. 2007;67:12007–17.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Rajendra G. Mehta.

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Mehta, R.G., Murillo, G., Naithani, R. et al. Cancer Chemoprevention by Natural Products: How Far Have We Come?. Pharm Res 27, 950–961 (2010). https://doi.org/10.1007/s11095-010-0085-y

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  • DOI: https://doi.org/10.1007/s11095-010-0085-y

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