Abstract B67: Influence of black cohosh and its isolated triterpenes on tamoxifen‐induced endometrial cell proliferation Free

The selective estrogen modulator tamoxifen has been proven efficacious in the treatment and prevention of breast cancer. However, tamoxifen treatment leads to consequences of estrogen deprivation including inducing menopausal hot flashes. In addition, tamoxifen causes enhanced endometrial cell proliferation resulting in an increased endometrial cancer risk. The latter effect is thought to be due to pro‐estrogenic effects specific to the endometrium. The botanical dietary supplement black cohosh (Cimicifuga racemosa) is frequently used for the alleviation of hot flashes in this high‐risk population. Black cohosh extracts contain antioxidative, antiproliferative, anti‐inflammatory, and detoxification enzyme inducing compounds. We therefore analyzed whether a standardized black cohosh extract or its isolated compounds prevent tamoxifen induced endometrial cell proliferation. First, we analyzed the influence of black cohosh on the proliferation in the Ishikawa endometrial cancer cell line with and without tamoxifen. At concentrations of 30 µg/mL black cohosh significantly decreased endometrial cell proliferation as measured by the SRB assay in the presence as well as in the absence of tamoxifen. Assaying various black cohosh fractions and isolated compounds revealed that a small sub‐fraction of the triterpenes contained within black cohosh were responsible for the observed activity. Both, the extract and its sub‐fraction, induced G1 cell cycle arrest. Next, we analyzed the influence of black cohosh extract on tamoxifen induced endometrial cell proliferation in an immature rat model. The results demonstrated that black cohosh extract did not influence tamoxifen's uterotrophic activity in vivo suggesting that the concentrations achieved in vivo with commonly used black cohosh doses are too low for this effect. Further analysis is ongoing to explore the potential of the isolated active compounds in preventing tamoxifen enhanced endometrial cancer risk.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B67.