Synergistic cytotoxic effects of tamoxifen and black cohosh on MCF-7 and MDA-MB-231 human breast cancer cells: an in vitro study

Breast cancer cell cultures were exposed to different concentrations of black cohosh, estradiol (E-2), and tamoxifen to examine the effect on cell proliferation; cytotoxicity was assessed by using sulforhodamine B (SRB) dye solution. E-2 (10(-10)-10(-8) mol/L) markedly stimulated the proliferation of MCF-7 cells (p < 0.01). Tamoxifen stimulated MCF-7 cell proliferation at 10(-6) mol/L and 10(-5) mol/L (p < 0.005) but inhibited in a dose-dependent fashion the proliferative effect of E-2 (p < 0.001). Black cohosh alone did not show any stimulatory effect, but exhibited a cytotoxic effect, which was significant at 10(3) mu g/mL (p < 0.001). Adding black cohosh at 10(0)-10(3) mu g/mL to E-2 at 10(-9) mol/L also resulted in a dose-dependent inhibition of E-2 proliferative effect. Interestingly, the combination of black cohosh (10(0)-10(3) ltg/mL) with increasing tamoxifen concentrations further inhibited MCF-7 cell growth. On MDA-MB-231 cells, neither E-2 nor tamoxifen displayed any detectable effect. However, black cohosh inhibited MDA-MB-231 cell proliferation at 10(3) mu g/mL (p < 0.05), and this inhibitory effect was enhanced by increasing tamoxifen concentrations. This study reveals a cytotoxic effect of black cohosh on both estrogen-sensitive and estrogen-insensitive breast cancer cells and a synergism with tamoxifen for inhibition of cancerous cell growth.