Soy Isoflavones May Hold Key To the Prevention Of Prostate Cancer

James meschino DC, MS, ROHP

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⁾

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).

References

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