Skip to main content

Human Cancer Chemoprevention: Hurdles and Challenges

  • Chapter
  • First Online:

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 329))

Abstract

Cancer is considered a disease of aging since the risk for developing the disease considerably increases with age. It is estimated that 77% of all cancers are diagnosed in people who fall within the age group of 55 or older. Also, it takes several years from initiation to the development of detectable cancer. One advantage of the long latency is that it provides numerous opportunities for intervention. While intervention approaches cannot be geared towards a whole population, they can nevertheless be directed towards a defined group of people who have a greater relative risk for developing the disease. The idea of cancer prevention through the use of nontoxic agents, preferably from dietary sources, has therefore emerged as an appropriate strategy for controlling the disease. An important aspect of chemoprevention is that agents can be designed for intervention at any stage during the multistage process of carcinogenesis. This process of slowing the progression of cancer is applicable to many cancers with long latency, including prostate cancer. Over the past two decades we have put considerable effort into identifying dietary substances in the form of extracts and pure compounds that can be used for the prevention of prostate and other cancers. Although cancer chemoprevention has proven to be a successful strategy in animals and, to some extent, we can say that the mission has been accomplished, its application to humans has met with limited success. This chapter will discuss various challenges associated with chemoprevention of cancer with the focus on studies with green tea and prostate cancer.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
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

Learn about institutional subscriptions

Abbreviations

CAM:

Complementary and alternative medicine

CI:

Confidence interval

COMT:

Catechol-O-methyltransferase

DNA:

Deoxyribose nucleic acid

EGC:

Epigallocatechin

EGCG:

(−)-Epigallocatechin gallate

FRET:

Fluorescence resonance energy transfer

GSTM1:

Glutathione S-transferase M1 gene

GTCs:

Green tea catechins

GTP:

Green tea polyphenols

HRPC:

Hormone refractory prostate cancer

IGF:

Insulin-like growth factor

JPHC:

Japanese Public Health Center

ODC:

Ornithine decarboxylase

PIN:

Prostatic intraepithelial neoplasia

PKC:

Protein kinase C

PSA:

Prostate specific antigen

SELECT:

Selenium and vitamin E cancer prevention trial

TRAMP:

Transgenic adenocarcinoma of the mouse prostate

References

  1. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10–29

    Article  Google Scholar 

  2. Sporn MB, Suh N (2000) Chemoprevention of cancer. Carcinogenesis 21:525–530

    Article  CAS  Google Scholar 

  3. Boone CW, Bacus JW, Bacus JV et al (1997) Properties of intraepithelial neoplasia relevant to the development of cancer chemopreventive agents. J Cell Biochem 28–29:1–20

    Article  Google Scholar 

  4. Adhami VM, Ahmad N, Mukhtar H (2003) Molecular targets for green tea in prostate cancer prevention. J Nutr 133:2417S–2424S

    CAS  Google Scholar 

  5. Siddiqui IA, Adhami VM, Saleem M et al (2006) Beneficial effects of tea and its polyphenols against prostate cancer. Mol Nutr Food Res 50:130–143

    Article  CAS  Google Scholar 

  6. Syed DN, Khan N, Afaq F, Mukhtar H (2007) Chemoprevention of prostate cancer through dietary agents: progress and promise. Cancer Epidemiol Biomarkers Prev 16:2193–2203

    Article  CAS  Google Scholar 

  7. Khan N, Afaq F, Mukhtar H (2008) Cancer chemoprevention through dietary antioxidants: progress and promise. Antioxid Redox Signal 10:475–510

    Article  CAS  Google Scholar 

  8. Klein EA (2005) Chemoprevention of prostate cancer. Crit Rev Oncol Hematol 54:1–10, Comfortable

    Article  Google Scholar 

  9. Lippman SM, Hawk ET (2009) Cancer prevention: from 1727 to milestones of the past 100 years. Cancer Res 69:5269–5284

    Article  CAS  Google Scholar 

  10. Wattenberg LW (1966) Chemoprophylaxis of carcinogenesis: a review. Cancer Res 26:1520–1526

    CAS  Google Scholar 

  11. Sporn MB, Dunlop NM, Newton DL et al (1976) Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed Proc 35:1332–1338

    CAS  Google Scholar 

  12. Sporn MB (1976) Approaches to prevention of epithelial cancer during the preneoplastic period. Cancer Res 36:2699–2702

    CAS  Google Scholar 

  13. Gescher A, Pastorino U, Plummer SM et al (1998) Suppression of tumour development by substances derived from the diet – mechanisms and clinical implications. Br J Clin Pharmacol 45:1–12

    Article  CAS  Google Scholar 

  14. Wattenberg LW (1985) Chemoprevention of cancer. Cancer Res 45:1–8

    Article  CAS  Google Scholar 

  15. Ip C, Ip MM (1981) Chemoprevention of mammary tumorigenesis by a combined regimen of selenium and vitamin A. Carcinogenesis 2:915–918

    Article  CAS  Google Scholar 

  16. Ip C (1981) Prophylaxis of mammary neoplasia by selenium supplementation in the initiation and promotion phases of chemical carcinogenesis. Cancer Res 41:4386–4390

    CAS  Google Scholar 

  17. Croft WA, Croft MA, Paulus KP et al (1981) 13-cis-Retinoic acid: effect on urinary bladder carcinogenesis by N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide in Fischer rats. Cancer Lett 12:355–360

    Article  CAS  Google Scholar 

  18. Thompson HJ, Chasteen ND, Meeker LD (1984) Dietary vanadyl(IV) sulfate inhibits chemically-induced mammary carcinogenesis. Carcinogenesis 5:849–851

    Article  CAS  Google Scholar 

  19. McCormick DL, Wilson AM (1986) Combination chemoprevention of rat mammary carcinogenesis by indomethacin and butylated hydroxytoluene. Cancer Res 46:3907–3911

    CAS  Google Scholar 

  20. Wattenberg LW, Bueding E (1986) Inhibitory effects of 5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione (Oltipraz) on carcinogenesis induced by benzo[a]pyrene, diethylnitrosamine and uracil mustard. Carcinogenesis 7:1379–1381

    Article  CAS  Google Scholar 

  21. Gunby P (1978) Retinoid chemoprevention trial begins against bladder cancer. JAMA 240:609–610

    Article  CAS  Google Scholar 

  22. Sim HG, Cheng CW (2005) Changing demography of prostate cancer in Asia. Eur J Cancer 41:834–845

    Article  Google Scholar 

  23. Angwafo FF (1998) Migration and prostate cancer: an international perspective. J Natl Med Assoc 90:S720–S723

    CAS  Google Scholar 

  24. Boyle P, Severi G (1999) Epidemiology of prostate cancer chemoprevention. Eur Urol 35:370–376

    Article  CAS  Google Scholar 

  25. Adlercreutz H (1990) Western diet and Western diseases: some hormonal and biochemical mechanisms and associations. Scand J Clin Lab Invest 201:3–23

    Article  CAS  Google Scholar 

  26. Schuurman AG, Goldbohm RA, Brants HA et al (2002) A prospective cohort study on intake of retinol, vitamins C and E, and carotenoids and prostate cancer risk (Netherlands). Cancer Causes Control 13:573–582

    Article  Google Scholar 

  27. Katiyar S, Mukhtar H (1996) Tea in chemoprevention of cancer. Int J Oncol 8:221–238

    CAS  Google Scholar 

  28. Wilding G (1995) Endocrine control of prostate cancer. Cancer Surv 23:43–62

    CAS  Google Scholar 

  29. Liao S, Hiipakka RA (1995) Selective inhibition of steroid 5 alpha-reductase isozymes by tea epicatechin-3-gallate and epigallocatechin-3-gallate. Biochem Biophys Res Commun 214:833–838

    Article  CAS  Google Scholar 

  30. Ren F, Zhang S, Mitchell SH et al (2000) Tea polyphenols down-regulate the expression of the androgen receptor in LNCaP prostate cancer cells. Oncogene 19:1924–1932

    Article  CAS  Google Scholar 

  31. Gupta S, Ahmad N, Mukhtar H (1999) Prostate cancer chemoprevention by green tea. Semin Urol Oncol 17:70–76

    CAS  Google Scholar 

  32. Gupta S, Ahmad N, Mohan RR et al (1999) Prostate cancer chemoprevention by green tea: in vitro and in vivo inhibition of testosterone-mediated induction of ornithine decarboxylase. Cancer Res 59:2115–2120

    CAS  Google Scholar 

  33. Siddiqui IA, Asim M, Hafeez BB et al (2011) Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer. FASEB J 25:1198–1207

    Article  CAS  Google Scholar 

  34. Khan N, Afaq F, Mukhtar H (2006) Apoptosis by dietary factors: the suicide solution for delaying cancer growth. Carcinogenesis 28:233–239

    Article  Google Scholar 

  35. Ahmad N, Feyes DK, Nieminen AL et al (1997) Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells. J Natl Cancer Inst 89:1881–1886

    Article  CAS  Google Scholar 

  36. Gupta S, Ahmad N, Nieminen AL et al (2000) Growth inhibition, cell-cycle dysregulation, and induction of apoptosis by green tea constituent (−)-epigallocatechin-3-gallate in androgen-sensitive and androgen-insensitive human prostate carcinoma cells. Toxicol Appl Pharmacol 164:82–90

    Article  CAS  Google Scholar 

  37. Gupta S, Hussain T, Mukhtar H (2003) Molecular pathway for (−)-epigallocatechin-3-gallate-induced cell cycle arrest and apoptosis of human prostate carcinoma cells. Arch Biochem Biophys 410:177–185

    Article  CAS  Google Scholar 

  38. Hastak K, Gupta S, Ahmad N et al (2003) Role of p53 and NF-kappaB in epigallocatechin-3-gallate-induced apoptosis of LNCaP cells. Oncogene 22:4851–4859

    Article  CAS  Google Scholar 

  39. Gupta S, Hastak K, Afaq F et al (2004) Essential role of caspases in epigallocatechin-3-gallate-mediated inhibition of nuclear factor kappa B and induction of apoptosis. Oncogene 23:2507–2522

    Article  CAS  Google Scholar 

  40. Hastak K, Agarwal MK, Mukhtar H et al (2005) Ablation of either p21 or Bax prevents p53-dependent apoptosis induced by green tea polyphenol epigallocatechin-3-gallate. FASEB J 19:789–791

    CAS  Google Scholar 

  41. Dou QP, Li B (1999) Proteasome inhibitors as potential novel anticancer agents. Drug Resist Updat 2:215–223

    Article  CAS  Google Scholar 

  42. Nam S, Smith DM, Dou QP (2001) Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo. J Biol Chem 276:13322–13330

    Article  CAS  Google Scholar 

  43. Smith DM, Wang Z, Kazi A et al (2002) Synthetic analogs of green tea polyphenols as proteasome inhibitors. Mol Med 8:382–392

    CAS  Google Scholar 

  44. Wang SI, Mukhtar H (2002) Gene expression profile in human prostate LNCaP cancer cells by epigallocatechin-3-gallate. Cancer Lett 182:43–51

    Article  CAS  Google Scholar 

  45. Livne E, Fishman DD (1997) Linking protein kinase C to cell-cycle control. Eur J Biochem 248:1–9

    Article  Google Scholar 

  46. Fishman DD, Segal S, Livneh E (1998) The role of protein kinase C in G1 and G2/M phases of the cell cycle. Int J Oncol 12:181–186

    CAS  Google Scholar 

  47. Gupta S, Hastak K, Ahmad N et al (2001) Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols. Proc Natl Acad Sci USA 98:10350–10355

    Article  CAS  Google Scholar 

  48. Jatoi A, Ellison N, Burch PA et al (2003) A phase II trial of green tea in the treatment of patients with androgen independent metastatic prostate carcinoma. Cancer 97:1442–1446

    Article  CAS  Google Scholar 

  49. Adhami VM, Siddiqui IA, Ahmad N et al (2004) Oral consumption of green tea polyphenols inhibits insulin-like growth factor-I-induced signaling in an autochthonous mouse model of prostate cancer. Cancer Res 64:8715–8722

    Article  CAS  Google Scholar 

  50. Caporali A, Davalli P, Astancolle S et al (2004) The chemopreventive action of catechins in the TRAMP mouse model of prostate carcinogenesis is accompanied by clusterin over-expression. Carcinogenesis 25:2217–2224

    Article  CAS  Google Scholar 

  51. Choan E, Segal R, Jonker D (2005) A prospective clinical trial of green tea for hormone refractory prostate cancer: an evaluation of the complementary/alternative therapy approach. Urol Oncol 23:108–113

    Article  CAS  Google Scholar 

  52. Bettuzzi S, Brausi M, Rizzi F et al (2006) Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res 66:1234–1240

    Article  CAS  Google Scholar 

  53. Harper CE, Patel BB, Wang J et al (2007) Epigallocatechin-3-gallate suppresses early stage, but not late stage prostate cancer in TRAMP mice: mechanisms of action. Prostate 67:1576–1589

    Article  CAS  Google Scholar 

  54. Brausi M, Rizzi F, Bettuzzi S (2008) Chemoprevention of human prostate cancer by green tea catechins: two years later. A follow-up update. Eur Urol 54:472–473

    Article  Google Scholar 

  55. Adhami VM, Siddiqui IA, Sarfaraz S et al (2009) Effective prostate cancer chemopreventive intervention with green tea polyphenols in the TRAMP model depends on the stage of the disease. Clin Cancer Res 15:1947–1953

    Article  CAS  Google Scholar 

  56. McLarty J, Bigelow RL, Smith M et al (2009) Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. Cancer Prev Res (Phila) 2:673–682

    Article  CAS  Google Scholar 

  57. Nguyen MM, Ahmann FR, Nagle RB et al (2012) Randomized, double-blind, placebo-controlled trial of polyphenon E in prostate cancer patients before prostatectomy: evaluation of potential chemopreventive activities. Cancer Prev Res (Phila) 5:290–298

    Article  CAS  Google Scholar 

  58. Liao S, Umekita Y, Guo J et al (1995) Growth inhibition and regression of human prostate and breast tumors in athymic mice by tea epigallocatechin gallate. Cancer Lett 96:239–243

    Article  CAS  Google Scholar 

  59. Roomi MW, Ivanov V, Kalinovsky T et al (2005) In vivo antitumor effect of ascorbic acid, lysine, proline and green tea extract on human prostate cancer PC-3 xenografts in nude mice: evaluation of tumor growth and immunohistochemistry. In Vivo 19:179–183

    CAS  Google Scholar 

  60. Siddiqui IA, Zaman N, Aziz MH et al (2006) Inhibition of CWR22Rν1 tumor growth and PSA secretion in athymic nude mice by green and black teas. Carcinogenesis 27:833–839

    Article  CAS  Google Scholar 

  61. Gingrich JR, Barrios RJ, Kattan MW et al (1997) Androgen-independent prostate cancer progression in the TRAMP model. Cancer Res 57:4687–4691

    CAS  Google Scholar 

  62. Kurahashi N, Sasazuki S, Iwasaki M et al (2008) Green tea consumption and prostate cancer risk in Japanese men: a prospective study. Am J Epidemiol 167:71–77

    Article  Google Scholar 

  63. Jian L, Lee AH, Binns CW (2007) Tea and lycopene protect against prostate cancer. Asia Pac J Clin Nutr 16:453–457

    CAS  Google Scholar 

  64. Jian L, Du CJ, Lee AH et al (2005) Do dietary lycopene and other carotenoids protect against prostate cancer? Int J Cancer 113:1010–1014

    Article  Google Scholar 

  65. Lippman SM, Klein EA, Goodman PJ et al (2009) Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the selenium and vitamin E cancer prevention trial (SELECT). JAMA 301:39–51

    Article  CAS  Google Scholar 

  66. Baron JA, Sandler RS, Bresalier RS et al (2006) A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. Gastroenterology 131:1674–1682

    Article  CAS  Google Scholar 

  67. Fisher B, Costantino JP, Wickerham DL et al (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90:1371–1388

    Article  CAS  Google Scholar 

  68. Kaplan SA, Roehrborn CG, Meehan AG et al (2009) Evidence that finasteride reduces risk of most frequently detected intermediate- and high-grade (Gleason score 6 and 7) cancer. Urology 73:935–939

    Article  Google Scholar 

  69. Elmets CA, Viner JL, Pentland AP et al (2010) Chemoprevention of nonmelanoma skin cancer with celecoxib: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst 102:1835–1844

    Article  CAS  Google Scholar 

  70. Wu AH, Tseng CC, Van Den Berg D et al (2003) Tea intake, COMT genotype, and breast cancer in Asian-American women. Cancer Res 63:7526–7529

    CAS  Google Scholar 

  71. Landis-Piwowar K, Chen D, Chan TH et al (2010) Inhibition of catechol-Omicron-methyltransferase activity in human breast cancer cells enhances the biological effect of the green tea polyphenol (−)-EGCG. Oncol Rep 24(2):563–569

    CAS  Google Scholar 

  72. Gasper AV, Al-Janobi A, Smith JA et al (2005) Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli. Am J Clin Nutr 82:1283–1291

    CAS  Google Scholar 

  73. Lampe JW (2009) Is equol the key to the efficacy of soy foods? Am J Clin Nutr 89:1664S–16647S

    Article  CAS  Google Scholar 

  74. DeWeerdt S (2011) Food: the omnivore’s labyrinth. Nature 471:S22–S24

    Article  CAS  Google Scholar 

  75. Maskarinec G, Noh JJ (2004) The effect of migration on cancer incidence among Japanese in Hawaii. Ethn Dis 14:431–439

    Google Scholar 

  76. Goss PE, Ingle JN, Alés-Martínez JE et al (2011) Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med 364:2381–2391

    Article  CAS  Google Scholar 

  77. Schmidt C (2011) The breast cancer chemoprevention debate. J Natl Cancer Inst 103:1646–1647

    Article  Google Scholar 

  78. Wu X, Lippman SM (2011) An intermittent approach for cancer chemoprevention. Nat Rev Cancer 11:879–885

    CAS  Google Scholar 

  79. Wu X, Patterson S, Hawk E (2011) Chemoprevention – history and general principles. Best Pract Res Clin Gastroenterol 25:445–459

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hasan Mukhtar .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Adhami, V.M., Mukhtar, H. (2012). Human Cancer Chemoprevention: Hurdles and Challenges. In: Pezzuto, J., Suh, N. (eds) Natural Products in Cancer Prevention and Therapy. Topics in Current Chemistry, vol 329. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2012_342

Download citation

Publish with us

Policies and ethics