Effects of phytoestrogens on the activity and growth of primary breast cancer cells ex vivo

Aim: To explore the ex vivo effects of phytoestrogens on primary human breast cancer cells. Methods: Breast cancer cells were obtained from patients who underwent primary breast cancer surgery, which were treated with 10⁻⁸ M 17β-estradiol (E₂), one of three phytoestrogens (genistein, resveratrol and quercetin, 10⁻⁷ M), and a combination of E₂ and one of the three phytoestrogens for 48 h. These cells were then extracted for viability and apoptosis assay. The proteins involved in the proliferative and apoptotic pathways were evaluated by western blot analysis. Results: Human breast cancer cell viability was inhibited by all phytoestrogens but induced by E₂ with or without phytoestrogen. Apoptotic cells, as well as the proteins involved in apoptotic pathway and estrogen receptor (ER) β, were significantly increased in the cells treated with phytoestrogen alone. The use of E₂ with or without a phytoestrogen revealed completely opposite results. The proteins involved in the proliferative pathway and ER α expression were all increased in the cultures with E₂ with or without phytoestrogens. Conclusion: In the presence of E₂, these phytoestrogens lose the effects of suppressing breast cancer cells; contrastingly, induce growth stimulatory effects by inhibiting apoptosis and stimulating proliferation in primary breast cancer cells. Thus, the effects of phytoestrogens on breast cancer should be considered as E₂ still present in breast cancer tissue.