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Flavonoid Compounds in the Prevention and Treatment of Prostate Cancer

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Prostate Cancer Methods and Protocols

Part of the book series: Methods in Molecular Medicineā„¢ ((MIMM,volume 81))

Abstract

Compounds based on a flavonoid (di-phenolic) ring structure are emerging as a potentially important new class of pharmaceutical compounds with a broad range of biological activities, most prominent of which is their potential role as anticancer agents.

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References

  1. Adlercreutz, H., Fotsis, T., Heikkinen, R., Dwyer, J. T., Woods, M., Goldin, B. R., and Gorbach, S. L. (1982) Excretion of the lignans enterolactone and enterodiol and of equol in omnivorous and vegetarian postmenopausal women and in women with breast cancerai. Lancet 2, 1295ā€“1299.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  2. Ekman, P. (1989) BPH epidemiology and risk factors. Prostate Suppl. 2, 23ā€“31.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  3. Dhom, G. (1991) Epidemiology of hormone-depending tumors, in Endocrine Dependent Tumors (Voigt, K. D. and Knabbe, C., eds.), Raven Press, New York, pp. 1ā€“42.

    Google ScholarĀ 

  4. Mills, P. K., Beeson, W. L., Phillips, R. L., and Fraser, G. E. (1989) Cohort study of diet, lifestyle, and prostate cancer in Adventist men. Cancer 64, 598ā€“604.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  5. Dunn, J. E. (1975) Cancer epidemiology in populations of the United Statesā€”with emphasis on Hawaii and Californiaā€”and Japan. Cancer Res. 35, 3240ā€“3245.

    PubMedĀ  CASĀ  Google ScholarĀ 

  6. Kolonel, L. N., Hankin, J. H., and Nomura, A. M. Y. (1986) Multiethnic studies of diet, nutrition and cancer in Hawaii, in Nutrition And Cancer (Hayashi, Y., ed.), Japanese Science Society Press, Tokyo, pp. 29ā€“40.

    Google ScholarĀ 

  7. Setchell, K. D. R. and Adlercreutz, H. (1988) Mammalian lignans and phytooestrogens. Recent studies on their formation, metabolism and biological role in health and disease, in Role of the Gut Flora in Toxicity and Cancer (Rowland, I. R., ed.), Academic Press Ltd, San Diego, pp. 315ā€“345.

    Google ScholarĀ 

  8. Kelly, G. E., Nelson, C., Waring, M. A., Joannou, G. E., and Reeder, A.Y. (1993) Metabolites of dietary (soya) isoflavones in human urine. Clin. Chim. Acta 223, 9ā€“22.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  9. Morton, M. S., Chan, P. S., Cheng, C., Blacklock, N., Matos-Ferreira, A., Abranches-Monteiro L., et al. (1997) Lignans and isoflavonoids in plasma and prostatic fluid in men: Samples from Portugal, Hong Kong, and the United Kingdom. Prostate 32, 122ā€“128.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  10. Miksicek, R. J. (1994) Interaction of naturally occurring nonsteroidal estrogens with expressed recombinant human estrogen receptor. J. Steroid Biochem. Mol. Biol. 49, 153ā€“160.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  11. Collins, B. M., McLachlan, J. A., and Arnold, S. F. (1997) The estrogenic and antiestrogenic activities of phytochemicals with human estrogen receptor expressed in yeast. Steroids 62, 365ā€“372.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  12. Miksicek, R. J. (1993) Commonly occurring plant flavonoids have estrogenic activity. Mol. Pharmacol. 44, 37ā€“43.

    PubMedĀ  CASĀ  Google ScholarĀ 

  13. Cato, A. C., Miksicek, R., Schutz, G., Arnemann, J., and Beato, M. (1086) The hormone regulatory element of mouse mammary tumour virus mediates progesterone induction. EMBO J. 5, 2237ā€“2240.

    Google ScholarĀ 

  14. Campbell, D. R. and Kurzer, M. S. (1993) Flavonoid inhibition of aromatase enzyme activity in human preadipocytes. J. Steroid Biochem. Mol. Biol. 46, 381ā€“388.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  15. Morton, M. S., Griffiths, K., and Blacklock, N. (1996) The preventive role of diet in prostatic disease. Br. J. Urol. 77, 481ā€“493.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  16. Evans, B. A., Griffiths, K., and Morton, M. S. (1995) Inhibition of 5 alpha-reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids. J. Endocrinol. 147, 295ā€“302.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  17. Bruchovsky, N. and Wilson, J. D. (1968) The conversion of testosterone to 5-alpha-androstan-17-beta-ol-3-one by rat prostate in vivo and in vitro. J. Biol. Chem. 243, 2012ā€“2021.

    PubMedĀ  CASĀ  Google ScholarĀ 

  18. Anderson, K. M. and Liao, S. (1968) Selective retention of dihydrotestosterone by prostatic nuclei. Nature 219, 277ā€“279.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  19. Ross, R. K., Bernstein, L., Lobo, R. A., Shimizu, H., Stanczyk, F. Z., Pike, M. C., and Henderson, B. E. (1992) 5-alpha-reductase activity and risk of prostate cancer among Japanese and US white and black males. Lancet 339, 887ā€“889.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  20. Keung, W. M. (1995) Dietary estrogenic isoflavones are potent inhibitors of beta-hydroxysteroid dehydrogenase of P. testosteronii. Biochem. Biophys. Res. Commun. 215, 1137ā€“1144.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  21. Wong, C. K. and Keung, W. M. (1997) Daidzein sulfoconjugates are potent inhibitors of sterol sulfatase (EC 3.1.6.2). Biochem. Biophys. Res. Commun. 233, 579ā€“583.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  22. Sun, X.Y., Plouzek, C. A., Henry, J. P., Wang, T. T., and Phang, J. M. (1998) Increased UDP-glucuronosyltransferase activity and decreased prostate specific antigen production by biochanin A in prostate cancer cells. Cancer Res. 58, 2379ā€“2384.

    PubMedĀ  CASĀ  Google ScholarĀ 

  23. Akiyama, T., Ishida, J., Nakagawa, S., Ogawara, H., Watanabe, S., Itoh, N., et al. (1987) Genistein, a specific inhibitor of tyrosine-specific protein kinases. J. Biol. Chem. 262, 5592ā€“5595.

    PubMedĀ  CASĀ  Google ScholarĀ 

  24. Suolinna, E. M., Lang, D. R., and Racker, E. (1974) Quercetin, an artificial regulator of the high aerobic glycolysis of tumor cells. J. Natl. Cancer Inst. 53, 1515ā€“1519.

    PubMedĀ  CASĀ  Google ScholarĀ 

  25. Shoshan, V. and MacLennan, D. H. (1981) Quercetin interaction with the (Ca2++ Mg2+)-ATPase of sarcoplasmic reticulum. J. Biol. Chem. 256, 887ā€“892.

    PubMedĀ  CASĀ  Google ScholarĀ 

  26. Ono, K., Nakane, H., Fukushima, M., Chermann, J. C., and Barre-Sinoussi, F. (1990) Differential inhibitory effects of various flavonoids on the activities of reverse transcriptase and cellular DNA and RNA polymerases. Eur. J. Biochem. 190, 469ā€“476.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  27. Glossmann, H., Presek, P., and Eigenbrodt, E. (1981) Quercetin inhibits tyrosine phosphorylation by the cyclic nucleotide-independent, transforming protein kinase, pp60src. Naunyn Schmiedebergs Arch. Pharmacol. 317, 100ā€“102.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  28. Matter, W. F., Brown, R. F., and Vlahos, C. J. (1992) The inhibition of phosphatidylinositol 3-kinase by quercetin and analogs. Biochem. Biophys. Res. Commun. 186, 624ā€“631.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  29. Prajda, N., Singhal, R. L., Yeh, Y. A., Olah, E., Look, K. Y., and Weber, G. (1995) Linkage of reduction in 1-phosphatidylinositol 4-kinase activity and inositol 1,4,5-trisphosphate concentration in human ovarian carcinoma cells treated with quercetin. Life Sci. 56, 1587ā€“1593.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  30. Rizzo, M. T. and Weber, G. (1994) 1-Phosphatidylinositol 4-kinase: an enzyme linked with proliferation and malignancy. Cancer Res. 54, 2611ā€“2614.

    PubMedĀ  CASĀ  Google ScholarĀ 

  31. Yoshida, M., Yamamoto, M., and Nikaido, T. (1992) Quercetin arrests human leukemic T-cells in late G1 phase of the cell cycle. Cancer Res. 52, 6676ā€“6681.

    PubMedĀ  CASĀ  Google ScholarĀ 

  32. Scambia, G., Ranelletti, F. O., Panici, P. B., Piantelli, M., Bonanno, G., De Vincenzo, R., et al. (1990) Inhibitory effect of quercetin on OVCA 433 cells and presence of type II oestrogen binding sites in primary ovarian tumours and cultured cells. Br. J. Cancer 62, 942ā€“946.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  33. Wei, Y. Q., Zhao, X., Kariya, Y., Fukata, H., Teshigawara, K., and Uchida, A. (1994) Induction of apoptosis by quercetin: involvement of heat shock protein. Cancer Res. 54, 4952ā€“4957.

    PubMedĀ  CASĀ  Google ScholarĀ 

  34. Avila, M. A., Velasco, J. A., Cansado, J., and Notario, V. (1994) Quercetin mediates the down-regulation of mutant p53 in the human breast cancer cell line MDA-MB468. Cancer Res. 54, 2424ā€“2428.

    PubMedĀ  CASĀ  Google ScholarĀ 

  35. Constantinou, A. and Huberman, E. (1995) Genistein as an inducer of tumor cell differentiation: Possible mechanisms of action. Proc. Soc. Exp. Biol. Med. 208, 109ā€“115.

    PubMedĀ  CASĀ  Google ScholarĀ 

  36. Traganos, F., Ardelt, B., Halko, N., Bruno, S., and Darzynkiewicz, Z. (1992) Effects of genistein on the growth and cell cycle progression of normal human lymphocytes and human leukemic MOLT-4 and HL-60 cells. Cancer Res. 52, 6200ā€“6208.

    PubMedĀ  CASĀ  Google ScholarĀ 

  37. Constantinou, A., Kiguchi, K., and Huberman, E. (1990) Induction of differentiation and DNA strand breakage in human HL-60 and K-562 leukemia cells by genistein. Cancer Res. 50, 2618ā€“2624.

    PubMedĀ  CASĀ  Google ScholarĀ 

  38. Peterson, G. and Barnes, S. (1991) Genistein inhibition of the growth of human breast cancer cells: Independence from estrogen receptors and the multi-drug resistance gene. Biochem. Biophys. Res. Commun. 179, 661ā€“667.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  39. Peterson, G. and Barnes, S. (1996) Genistein inhibits both estrogen and growth factor-stimulated proliferation of human breast cancer cells. Cell Growth Differ. 7, 1345ā€“1351.

    PubMedĀ  CASĀ  Google ScholarĀ 

  40. Monti, E. and Sinha, B. K. (1994) Antiproliferative effect of genistein and adriamycin against estrogen-dependent and-independent human breast carcinoma cell lines. Anticancer Res. 14, 1221ā€“1226.

    PubMedĀ  CASĀ  Google ScholarĀ 

  41. Pagliacci, M. C., Smacchia, M., Migliorati, G., Grignani, F., Riccardi, C., and Nicoletti, I. (1994) Growth-inhibitory effects of the natural phyto-oestrogen genistein in MCF-7 human breast cancer cells. Eur. J. Cancer 30A, 1675ā€“1682.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  42. Matsukawa, Y., Marui, N., Sakai, T., Satomi, Y., Yoshida, M., Matsumoto, K., et al. (1993) Genistein arrests cell cycle progression at G2-M. Cancer Res. 53, 1328ā€“1331.

    PubMedĀ  CASĀ  Google ScholarĀ 

  43. Yanagihara, K., Ito, A., Toge, T., and Numoto, M. (1993) Antiproliferative effects of isoflavones on human cancer cell lines established from the gastrointestinal tract. Cancer Res. 53, 5815ā€“5821.

    PubMedĀ  CASĀ  Google ScholarĀ 

  44. Peterson, G. and Barnes, S. (1993) Genistein and biochanin A inhibit the growth of human prostate cancer cells but not epidermal growth factor receptor tyrosine autophosphorylation. Prostate 22, 335ā€“345.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  45. Schweigerer, L., Christeleit, K., Fleischmann, G., Adlercreutz, H., Wahala, K., Hase, T., et al. (1992) Identification in human urine of a natural growth inhibitor for cells derived from solid paediatric tumours. Eur. J. Clin. Invest. 22, 260ā€“264.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  46. Akiyama, T. and Ogawara, H. (1991) Use and specificity of genistein as inhibitor of protein-tyrosine kinases. Methods Enzymol. 201, 362ā€“370.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  47. Constantinou, A., Mehta, R., Runyan, C., Rao, K., Vaughan, A., and Moon, R. (1995) Flavonoids as DNA topoisomerase antagonists and poisons: structure-activity relationships. J. Natural Products 58, 217ā€“225.

    ArticleĀ  CASĀ  Google ScholarĀ 

  48. Watanabe, T., Kondo, K., and Oishi, M. (1991) Induction of in vitro differentiation of mouse erythroleukemia cells by genistein, an inhibitor of tyrosine protein kinases. Cancer Res. 51, 764ā€“768.

    PubMedĀ  CASĀ  Google ScholarĀ 

  49. Uckun, F. M., Evans, W. E., Forsyth, C. J., Waddick, K. G., Ahlgren, L. T., Chelstrom, L. M., et al. (1995) Biotherapy of B-cell precursor leukemia by targeting genistein to CD19-associated tyrosine kinases. Science 267, 886ā€“891.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  50. Fotsis, T., Pepper, M., Adlercreutz, H., Hase, T., Montesano, R., and Schweigerer, L. (1995) Genistein, a dietary ingested isoflavonoid, inhibits cell proliferation and in vitro angiogenesis. J. Nutr. 125(3 Suppl), 790Sā€“797S.

    PubMedĀ  CASĀ  Google ScholarĀ 

  51. Bergan, R., Kyle, E., Nguyen, P., Trepel, J., Ingui, C., and Neckers, L. (1996) Genistein-stimulated adherence of prostate cancer cells is associated with the binding of focal adhesion kinase to beta-1-integrin. Clin. Exp. Metastasis 14, 389ā€“398.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  52. Carlson, B. A., Dubay, M. M., Sausville, E. A., Brizuela, L., and Worland, P. J. (1996) Flavopiridol induces G1 arrest with inhibition of cyclin-dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells. Cancer Res. 56, 2973ā€“2978.

    PubMedĀ  CASĀ  Google ScholarĀ 

  53. Shapiro, G. I., Koestner, D. A., Matranga, C. B., and Rollins, B. J. (1999) Flavopiridol induces cell cycle arrest and p53-independent apoptosis in non-small cell lung cancer cell lines. Clin. Cancer Res. 5, 2925ā€“2938.

    PubMedĀ  CASĀ  Google ScholarĀ 

  54. Drees, M., Dengler, W. A., Roth, T., Labonte, H., Mayo, J., Malspeis, L., et al. (1997) Flavopiridol (L86-8275): selective antitumor activity in vitro and activity in vivo for prostate carcinoma cells. Clin. Cancer Res. 3, 273ā€“279.

    PubMedĀ  CASĀ  Google ScholarĀ 

  55. Axelson, M., Kirk, D. N., Farrant, R. D., Cooley, G., Lawson, A. M., and Setchell, K. D. (1982) The identification of the weak oestrogen equol [7-hydroxy-3-(4ā€²-hydroxyphenyl)chroman] in human urine. Biochem. J. 201, 353ā€“357.

    PubMedĀ  CASĀ  Google ScholarĀ 

  56. Bannwart, C., Adlercreutz, H., Wahala, K., Kotiaho, T., Hesso, A., Brunow, G., and Hase, T. (1988) Identification of the phyto-oestrogen 3ā€²,7-dihydroxyisoflavan, an isomer of equol, in human urine and cowā€™s milk. Biomed. Environ. Mass Spectrom. 17, 1ā€“6.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  57. Joannou, G. E., Kelly, G. E., Reeder, A. Y., Waring, M., and Nelson, C. (1995) A urinary profile study of dietary phytoestrogens. The identification and mode of metabolism of new isoflavonoids. J. Steroid Biochem. Mol. Biol. 54, 167ā€“184.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  58. Bannwart, C., Fotsis, T., Heikkinen, R., and Adlercreutz, H. (1984) Identification of the isoflavonic phytoestrogen daidzein in human urine. Clin. Chim. Acta 136, 165ā€“172.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  59. Kok, J. W., Veldman, R. J., Klappe, K., Koning, H., Filipeanu, C. M., and Muller, M. (2000) Differential expression of sphingolipids in MRP1 overexpressing HT29 cells. Int. J. Cancer 87, 172ā€“178.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  60. Makela, S., Davis, V. L., Tally, W. C., Korkman, J., Salo, L., Vihko, R., et al. (1994) Dietary estrogens act through estrogen receptor-mediated processes and show no antiestrogenicity in cultured breast cancer cells. Environ. Health Perspect. 102, 572ā€“578.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  61. Wang, C. and Kurzer, M. S. (1997) Phytoestrogen concentration determines effects on DNA synthesis in human breast cancer cells. Nutr. Cancer 28, 236ā€“247.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  62. Setchell, K. D., Borriello, S. P., Hulme, P., Kirk, D. N., and Axelson, M. (1984) Nonsteroidal estrogens of dietary origin: possible roles in hormone-dependent disease. Am. J. Clin. Nutr. 40, 569ā€“578.

    PubMedĀ  CASĀ  Google ScholarĀ 

  63. Ingram, D., Sander, K., Kolybaba, M., and Lopez, D. (1998) Case-control study of phyto-oestrogens and breast cancer. Lancet 350, 990ā€“994.

    ArticleĀ  Google ScholarĀ 

  64. Adlercreutz, H., Goldin, B. R., Gorbach, S. L., Hockerstedt, K. A., Watanabe, S., Hamalainen, E. K., et al. (1995) Soybean phytoestrogen intake and cancer risk. J. Nutr. 125(3 Suppl), 757Sā€“770S.

    PubMedĀ  CASĀ  Google ScholarĀ 

  65. Martin, P. M., Horwitz, K. B., Ryan, D. S., and McGuire, W. L. (1978) Phytoestrogen interaction with estrogen receptors in human breast cancer cells. Endocrinology 103, 1860ā€“1867.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  66. Zhou, H., Goldman, M., Wu, J., Woestenborghs, R., Hassell, A.E., Lee, P., et al. (1998) A pharmacokinetic study of intravenous itraconazole followed by oral administration of itraconazole capsules in patients with advanced human immunodeficiency virus infection. J. Clin. Pharmacol. 38, 593ā€“602.

    PubMedĀ  CASĀ  Google ScholarĀ 

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Kelly, G.E., Husband, A.J. (2003). Flavonoid Compounds in the Prevention and Treatment of Prostate Cancer. In: Russell, P.J., Jackson, P., Kingsley, E.A. (eds) Prostate Cancer Methods and Protocols. Methods in Molecular Medicineā„¢, vol 81. Springer, Totowa, NJ. https://doi.org/10.1385/1-59259-372-0:377

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  • DOI: https://doi.org/10.1385/1-59259-372-0:377

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