Pharmaceutical Research

, Volume 27, Issue 6, pp 950–961 | Cite as

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

  • Rajendra G. MehtaEmail author
  • Genoveva Murillo
  • Rajesh Naithani
  • Xinjian Peng
Expert Review


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.


chemoprevention natural products phytochemicals signaling 


  1. 1.
    Karpozilos A, Pavlidis N. The treatment of cancer in Greek antiquity. Eur J Cancer. 2004;40:2033–40.CrossRefPubMedGoogle Scholar
  2. 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.CrossRefPubMedGoogle Scholar
  3. 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.PubMedGoogle Scholar
  4. 4.
    Murillo G, Mehta RG. Cruciferous vegetables and cancer prevention. Nutr Cancer. 2001;41:17–28.CrossRefPubMedGoogle Scholar
  5. 5.
    Ambrosone CB, Tang L. Cruciferous vegetable intake and cancer prevention: role of nutrigenetics. Cancer Prev Res. 2009;2:298–300.CrossRefGoogle Scholar
  6. 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.CrossRefPubMedGoogle Scholar
  7. 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.CrossRefPubMedGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedGoogle Scholar
  11. 11.
    Balachandran P, Govindrajan R. Cancer an Ayurvedic perspective. Pharmacol Res. 2005;51:19–30.PubMedGoogle Scholar
  12. 12.
    Xutian S, Zhang J, Louise W. New exploration and understanding of traditional Chinese medicine. Am J Chin Med. 2009;37:411–26.CrossRefPubMedGoogle Scholar
  13. 13.
    Kunow MA. Maya Medicine: traditional healing in Yucatan. New Mexico: University of New Mexico Press; 2003.Google Scholar
  14. 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.CrossRefGoogle Scholar
  15. 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.PubMedGoogle Scholar
  16. 16.
    Wattenberg LW. Inhibition of carcinogenesis by minor a nutrient constituents of the diet. Proc Nutr Soc. 1990;49:173–83.CrossRefPubMedGoogle Scholar
  17. 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.CrossRefGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 19.
    Singh RP, Agarwal R. Prostate cancer chemoprevention by silibinin: bench to bedside. Mol Carcinog. 2006;45:436–42.CrossRefPubMedGoogle Scholar
  20. 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.CrossRefGoogle Scholar
  21. 21.
    Guilford JM, Pezzuto JM. Natural products as inhibitors of carcinogenesis. Expert Opin Investig Drugs. 2008;17:1341–52.CrossRefPubMedGoogle Scholar
  22. 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.CrossRefPubMedGoogle Scholar
  23. 23.
    Kosmeder 2nd JW, Pezzuto JM. Novel plant derived anticarcinogens. IARC Sci Publ Rev. 2002;156:343–7.Google Scholar
  24. 24.
    Lippman SM, Hawk ET. Cancer prevention: from 1727 to milestones of the past 100 years. Cancer Res. 2009;69:5269–84.CrossRefPubMedGoogle Scholar
  25. 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.PubMedGoogle Scholar
  26. 26.
    Milner JA. Nutrition and cancer: essential elements for a roadmap. Cancer Lett. 2008;269:189–98.CrossRefPubMedGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.CrossRefPubMedGoogle Scholar
  30. 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. 31.
    Stoner GD. Foodstuffs for preventing cancer: the preclinical and clinical development of berries. Cancer Res. 2009;2:187–94.Google Scholar
  32. 32.
    Andreassen PR, Ho GP, D’Andrea AD. DNA damage responses and their many interactions with the replication fork. Carcinogenesis. 2006;27:883–92.CrossRefPubMedGoogle Scholar
  33. 33.
    Khan N, Afaq F, Mukhtar H. Apoptosis by dietary factors: the suicide solution for delaying cancer growth. Carcinogenesis. 2007;28:233–9.CrossRefPubMedGoogle Scholar
  34. 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.PubMedGoogle Scholar
  35. 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.CrossRefPubMedGoogle Scholar
  36. 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.CrossRefPubMedGoogle Scholar
  37. 37.
    Ahmed FE. Role of miRNA in carcinogenesis and biomarker selection: a methodological view. Expert Rev Mol Diagn. 2007;7:569–603.CrossRefPubMedGoogle Scholar
  38. 38.
    Lee YS, Dutta A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev. 2007;21:1025–30.CrossRefPubMedGoogle Scholar
  39. 39.
    Davis CD, Ross SA. Evidence for dietary regulation of microRNA expression in cancer cells. Nutr Rev. 2008;66:477–82.CrossRefPubMedGoogle Scholar
  40. 40.
    Marsit CJ, Eddy K, Kelsey KT. MicroRNA responses to cellular stress. Cancer Res. 2006;66:10843–8.CrossRefPubMedGoogle Scholar
  41. 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.CrossRefPubMedGoogle Scholar
  42. 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.CrossRefPubMedGoogle Scholar
  43. 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. 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. 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.CrossRefPubMedGoogle Scholar
  46. 46.
    Teskac K, Kristi J. The evidence for solid lipid nanoparticles mediated cell uptake of resveratrol Int J Pharmacol. 2009; PMID 19833178.Google Scholar
  47. 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.CrossRefGoogle Scholar
  48. 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.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Rajendra G. Mehta
    • 1
    • 2
    Email author
  • Genoveva Murillo
    • 1
  • Rajesh Naithani
    • 2
  • Xinjian Peng
    • 1
  1. 1.Carcinogenesis and Chemoprevention DivisionIIT Research InstituteChicago60616USA
  2. 2.Drug Discovery DivisionIIT Research InstituteChicagoUSA

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