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Soy Isoflavones May Hold Key To the Prevention Of Prostate Cancer


- by Dr. James Meschino, DC, MS, ROHP

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Intoduction

Prostate cancer is one of the most common cancers to affect men in Western countries (the leading cancer in U.S. and Canadian men), whereas in Africa, Eastern Europe, and Japan the risk of this disease remains low. Dietary and lifestyle factors appear to influence the development of this disease as migration studies indicate that a marked increase in prostate (and breast) cancer incidence occurs in persons that migrate from low- to high-risk geographical areas. Another intriguing fact is that postmortem evaluation indicates that the prevalence of latent (existing, but not manifest) prostate cancer is similar between high- and low-risk populations, with genetic and lifestyle factors implicated in the progression to the malignant form of the disease. Thus, by age 50, 15 to 30% of men have cancer cells present within the prostate gland regardless of where they reside. However, in low risk regions these cancer cells tend not to undergo promotion and progression to a clinically significant malignant state, but rather tend to remain dormant and non-life threatening. It is argued that certain dietary behaviors are directly involved in preventing the development of prostate cancer and/or prevent the further progression of latent prostate cancer. Intensive investigation has strongly suggested that soy isoflavones are one of the important dietary agents that appear to offer protection against prostate cancer. (1,2) In fact, a recent study using modern analytical technology to analyze dietary intakes of individual phytoestrogens in patients with prostate cancer or control subjects (cancer-free) indicated a significant protective effect of the soy isoflavones genistein and diadzein, as well as the phytoestrogen coumestrol. (3)

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Soy Isoflavones May Hold Key To the Prevention Of Prostate Cancer

Dr. James Meschino, 

DC, MS, ROHP

Soy Isoflavones (Genistein and Diadzein) May Defend Against Prostate Cancer

Research in this area reveals that there are at least seven modes of action through which soy isoflavones (genistein and diadzein) may defend against prostate cancer:

  1. Anti-proliferative-soy isoflavones have been shown to inhibit two key enzymes within prostate cancer cells that trigger cell division and growth. These two enzymes include protein tyrosine kinase and topoismerase II. By blocking their activity soy isoflavones have demonstrated an impressive ability to greatly inhibit the growth and division of prostate cancer cells under experimental conditions. (4,5,6).
  2. Increase sex hormone-binding globulin-soy isoflavones stimulate the synthesis of sex hormone-binding globulin in vivo, thus reducing the plasma concentration of free, unbound sex hormones. As a result there is less available (unbound) testosterone and other steroid compounds that are free to bind to prostate receptors and exert their potentially hyperproliferative effects. It is well established that certain androgens and estrogens are linked to the progression and promotion of prostate cancer and higher serum levels of sex hormone-binding globulin is associated with a reduced risk of many hormone dependent cancers. (7,8).
  3. Decreased steroid hormone synthesis-soy isoflavones have demonstrated the ability to help block the over production of certain steroid hormones that influence the promotion and progression of prostate cancer. Specifically, soy isoflavones are known to inhibit 5 alpha-reductase, aromatase (estrogen synthase) and the 17 beta-hydroxysteroid deydrogenase enzymes, which in turn block the synthesis (to an appreciable degree) of dihydrotestosterone, estrone and other steroid hormones, respectively. Dihydrotestosterone is known to enhance prostate cell division (including cancer cells) and is directly linked to the promotion and progression of prostate cancer in humans. The over production of estrogen hormone from adipose tissue is also associated with increased prostate cell proliferation and prostate cancer. (9,10,11).
  4. Antioxidant function-genistein, the most intensively researched soy isoflavoinoid, also acts as a cellular antioxidant. As soy isoflavones are known to concentrate within prostatic fluids (at higher values than in plasma), they are considered to be an important defense against free radical damage and the cancerous mutations that are known to arise from free radical damage to prostate cells. (12,13,14).
  5. Apoptosis: Soy isoflavones have also been shown to selectively encourage prostate cancer cells to undergo programmed cell death (apoptosis). In particular genistein has been shown to inhibit cell growth and induce apoptosis by modulating transforming growth factor-beta signaling pathways. This effect has been clearly shown with both LNCaP and PC-3 human prostate cancer cell lines. (15,16).
  6. Anti-angiogenisis: Soy isoflavones demonstrate an ability to hinder the ability of cancer cells from growing the necessary capillaries that feed their growth as they attempt to spread (metastasize) to adjacent tissues. It appears that genistein, in particular, blocks the synthesis and/or release of growth factors required to form the extensive network of blood vessels necessary to aid the spread of the malignancy. (17,18).
  7. Androgen blockade: Soy isoflavones bind to androgen and estrogen receptors on the prostate gland, partially blocking access to the cell of testosterone, estrone and related hormone modulators of prostate cell (and prostate cancer cell) growth. The net effect appears to be a down-regulation influence whereby the growth and cell division rate of prostate cells is slowed and any existing prostate cancer cells are subjected to less of a stimulatory influence from various androgens and estrogens (due to lower intracellular concentrations). (19) This effect is readily apparent from studies that demonstrate that genistein inhibits the growth of benign prostate hypertrophy, prostate cancer tissue in histoculture (20) and growth of tumor cell implants in rats. (21)

By all accounts sufficient evidence now exists to encourage the more frequent consumption of foods, supplements and nutraceuticals that are a rich source of soy isoflavones as a means to help prevent prostate cancer. Moreover, soy isoflavones may also be considered not only in a chemo preventive role, but possibly as chemotherapeutic agents as well. A recent report in the scientific literature indicated that in a case study, a 66-year old prostate cancer patient took a phytoestrogens supplement (160 mg per day) for one week before radical prostatectomy. On histological examination of the prostatectomy specimen, significant apoptosis in tumor cells suggestive of tumor regression was evident compared with the preoperative needle biopsy. (22)

From the stand point of prostate cancer prevention the traditional Asian diet contains an average isoflavone content of 50mg per day. Epidemiological data indicate that the incidence of clinically important prostate cancer is 80% less in Japan than in Canada and the United States. (2,23,24)

In summary, the body of evidence strongly suggests that men should consume sufficient soy products on a daily basis to yield a minimum of 50 mg of isoflavones as one means of prostate cancer chemoprevention. Soy isoflavones can be consumed from soy-based foods, supplements containing soy extract, and various soy-based functional foods (e.g. soy protein shake mix).

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Soy Isoflavones May Hold Key To the Prevention Of Prostate Cancer

Dr. James Meschino, 

DC, MS, ROHP

References

1.Yatani, R, Kusano, I, Shiraishi, T, Haysahi, T, and Stemmerman, GN: Latent prostate carcinoma: pathological and epidemiological aspects. Jpn J Clin Oncol 19, 319-326, 1989
2.Mitchell, J, et al. Effects of phytoestrogens on growth and DNA integrity in human prostate tumor cell lines: PC-3 and LNCaP. Nutr and Cancer, 2000: 38, 2: 223-228
3.Strom, SS, Yamamura, Y, Duporne, CM, Spitz, MR, Bahsain, RJ, et al: Phytoestrogen intake and prostate cancer: a case-control study using a new database. Nutr Cancer 33, 20-25, 1999
4.Akiyama, T, Ishida, J, Nakagawa, S, Ogawara, H, Watanabe, S, et al: Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 262, 5592-5595, 1987
5.Kaufman, W: Human topoismerase II function, tyrosine phosphatydilation and cell cycle check points. Proc Soc Exp Biol med 289, 327-334, 1998
6.Constantinou, A, and Huberman, E: Genistein as an inducer of tumor cell differentiation: possible mechanisms of action. Proc Soc Exp Biol Med, 206, 109-115, 1995
7.Adlercreutz, H, Hockerstedt, K, Baanwart, C, Bloigu, S, Hamalainea, E, et al: Effect of dietary components, including lignans and phytoestrogens, on enterophepatic circulation and liver metabolism of estrogens, and on sex hormone-binding globulin (SHBG). J Steriod Biochem 27, 1135-1144, 1987
8.Adlercreutz, H, Hockerstedt, K, Baanwart, C, Hamalainea, E, Fotsis, T, et al: Association between dietary fibre, urinary excretion of lignans and isoflavosic phytoestrogens, and plasma non-protein bound sex hormones in relation to breast cancer. In Progress in Cancer Research and Therapy: Hormones and Cancer, P Bresciani, RJB King, ME Lippman, and JP Raynaud (eds.) New York: Raven, 1988, vol 3, chapt 35, pp. 409-412
9.Makela, S, Poutanes, M, Lehtimaki, J, Kostian, MI, Santi, R, et al: Estrogen-specific 176-hydroxysteroid oxidoreduotase type I (EC 1.1.1.62) as a possible target for the action of phytoestrogens. Proc Soc Exp Biol med 208, 51-59, 1995
10.Evans, BAJ, Griffiths, K, and Morton, MS: Inhibition of 5a-reductase in genital skin fibroblasts and prostate tissue by lignans and isoflavonoids. J Endocrinol 147, 295-302, 1995
11.Wang, C, Makela, T, Hase, T, Adlercreutz, H, and Mindy, MS: Lignans and flavonoids inhibit aromatase enzyme in human preadipocytes, Steroid Biochem Mol Biol 50, 205-212, 1994
12.Messina, M et al. First International Symposium on the role of soy in preventing and treating chronic disease. J Nutr 1995, 125 (suppl): 5675-8085
13.Wei, H, Bowen, R, Cai, Q, Barnes, S, and Wang, Y: P Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Exp Biol Med 206, 124-130, 1995
14.Mitchell, JH, Gardner, PT, McPhail, DB, Morrice, PC, Collins, AR, et al: Antioxidant efficacy of phytoestrogens in chemical and biological model systems. Arch Biochem Biophys 360, 142-148, 1998
15.Kime, H, Peterson, TG, and Barnes S: Mechanisms of action of the soy isoflavone genistein: emerging role for its effects via transforming growth factor-B-signaling pathways. Am J Clin Nutr, 68, S1418-1425, 1998
16.Sathymoorthy, N, Gilsdorf, JS, and Wang, TTY: Differential effects of genistein on transforming growth factor-B1 expression in normal and malignant mammary epithelial cells. Anticancer Res: 18, 2449-2453 1998
17.Fotsis, T, et al. Genistein, a dietary derived inhibitor of in vitro antiogenesis. Proc Natl Acad Sci USA, 1993, 90: 2690-2694
18.Steele, VE , et al., Cancer chemoprevention agent development strategies for genistein. J Nutr. 1995, 125: 7135-7165
19.Pollard, M, et al. Influence of isoflavones in soy protein isolates on development of induced prostate-related cancers in L-W rats. Nutr and Cancer. 1997: 28, 1: 41-45
20.Schleicher, T, Zheng, M, Shang, M and Lamartiniere, CA: Genistein inhibition of prostate cancer cell growth and metastasis in vivo (abstract) Am J Clin Nutr 68 Suppl, 15268, 1998
21.Geller, J, Sionit, L, Partido, C, Li, L, Tan, X, et al: Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture Prostate 34, 75-79, 1998
22.Stephens, FO: Phytoestrogens and prostate cancer: possible preventive role. Med J Aust 167, 138-140, 1997
23.Armstrong, B, et al. Environmental factors and cancer incidence and mortality in different countries, with special references to dietary practices. Int J Cancer, 1975; 15: 617-631
24.Haenszel, W, et al. Studies of Japanese migrants. Mortality from cancer and other diseases among Japanese in the United States. J Natl Cancer Inst., 1968; 40: 43-68 

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