The combination of soy and green tea bioactive components synergistically prevents mammary carcinogenesis and inhibits angiogenesis in vivo.

A216

Breast cancer is the third most commonly diagnosed carcinoma in the world. Epidemiological investigation has suggested that lifestyle change, such as diet and nutrition, plays an important role in breast cancer development and progression. Dietary modification has been considered to be an effective regimen for breast cancer prevention. It has been realized that the effective cancer prevention activity of dietary components may result from interactions among several components that potentiate the activities of any single constituent. Our previous studies have suggested that the combination of soy and green tea significantly inhibited the growth of estrogen-dependent breast tumors in a synergistic manner in clinically relevant orthotopic tumor models. The objectives of our ongoing studies were to further evaluate the effects of soy and green tea combination on the prevention of mammary carcinogenesis in a transgenic mouse model and to evaluate the anti-angiogenesis activity of active soy and green tea components in vitro and in vivo. The 5-week-old female C3(1)/SV40 Tag transgenic mice were randomly assigned into experimental groups (n=12/group) and consumed one of the following experimental diets: (i) AIN-93 as the control, (ii) AIN-93 with addition of soy phytochemical concentrate (SPC) at 0.5% of the diet, (iii) AIN-93 with 1.0% green tea infusion in place of drinking water, or (iv) AIN-93 with SPC and green tea infusion. Food intake and body weight were measured weekly, and tumor appearance was monitored weekly. Twenty weeks after dietary treatments, the tumor incidences in mice treated with the control, SPC, green tea, and SPC and green tea combination are 58%, 58%, 33% and 25%, respectively. The results suggest that the SPC and green tea combination may also prevent mammary carcinogenesis in a synergistic manner. In vitro studies showed that soy isoflavone genistein and green tea polyphenols epigallocatechin gallate (EGCG) significantly inhibited endothelial cell proliferation, migration and tube formation, and the combination of genistein and EGCG had synergistic anti-angiogenesis activity. The Matrigel plug assay also showed that SPC and green tea, alone and in combination, inhibited angiogenesis in vivo. Our results suggest that the soy and green tea combination may prevent mammary carcinogenesis in a synergistic manner in part via combined effects on angiogenesis inhibition. Supported in part by the Susan G. Komen Breast Cancer Research Foundation (BCTR0202014, BCTR0402749) and the NIH/NCCAM (RO1AT00863).