Written by Susan Sweeny Johnson, PhD, Biochem. Sixty mice were fed varying levels of genistein, a soy isoflavone. Those receiving 250mg/kg had only 4% of the prostate tumors as the group with no genistein.

Genistein is an isoflavone found in soybeans which has phytoestrogen properties and is a powerful antioxidant. (Phytoestrogens are compounds from plants that bind to different estrogen receptors in humans.) The blood levels of genistein in soy consumers are almost 100 times that of non-soy consumers (1, 2). Previous studies have shown that Southeast Asians that eat soy have a prostate cancer mortality rate about 10 times lower than non-soy-consuming Westerners but these levels rise to near Western rates after immigration (3, 4). In these studies, the mortality rate correlates with blood genistein concentrations suggesting a dietary connection.

Death from prostate cancer is caused by metastasis (the breaking off of cancer cells from the primary tumor which travel to other body sites where new tumors then grow (5). There is no current effective means of inhibiting prostate metastasis according to these researchers.

In this study, sixty mice were fed either 0, 100 or 250 mg of genistein per kg of total food for five weeks. After one week, primary prostate tumors were inserted in the prostate area. Complete analysis of the mice was performed at four weeks. Final blood concentrations of genistein of the mice on the 100 mg/ kg diet were at the level measured in soy-consuming Japanese men (2). Blood concentrations of genistein approached the level achieved in clinical trials in the 250 mg/kg diet group (4). Metastases were found in the lungs and lymph nodes of mice after four weeks. The group of mice on the 100 mg/kg diet had 44+ 9 % of the lung metastases of the control (0 mg/kg genistein) and the 250 mg/kg diet group had 4 + 1% of the metastases of the control. These decreases were statistically significant (p< 0.05). Tumor volume, however, was unchanged.

Further studies were performed to determine the step at which genistein acts in preventing metastasis. Microscopic examination of cultured prostate tumor cells showed a distinct flattening in shape with the addition of genistein indicating that genistein acts to prevent the cell shape changes that occur prior to metastasis.

Also, genistein increased the number of proteins the tumor cells produced that stimulate metastasis but it also inhibited the activation of these proteins which occurs via phosphorylation (the addition of phosphate groups). The authors suggest that the prostate tumor cells try to compensate for the inihibition of metastasis by producing more metastatic proteins but these proteins are still not activated in the presence of genistein.

This research group has moved on to human prostate cancer studies on the effectiveness of genistein in preventing metastasis, completing phase I trials (6) and moving on to phase II trials.

Prostate cancer is the second most common cause of cancer deaths in American men (7) and costs Americans $1.3 billion per year according to a recent NIH report (8). In 2006, it is estimated that over 230,000 new cases of prostate cancer and over 27,000 deaths will be reported in the United States (9).

Source: Lakshman, Minalini, Li Xu, Vijayalakshmi Ananthanarayanan, Joshua Cooper, Chris H. Takimoto, Irene Helenowski, Jill C. Pelling, and Raymond C. Bergan. “Dietary genistein inhibits metastasis of human prostate cancer in mice.” Cancer research 68, no. 6 (2008): 2024-2032.

© 2008 American Association for Cancer Research

Posted August 8, 2008.

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