A dietary supplement for female sexual dysfunction, Avlimil, stimulates the growth of estrogen-dependent breast tumors (MCF-7) implanted in ovariectomized athymic nude mice

Avlimil, a dietary supplement advertised to ameliorate female sexual dysfunction, is a mixture of eleven herbal components, and some herbal constituents of Avlimil (including black cohosh, licorice, red raspberry, red clover and kudzu) contain phenolic compounds, which are suggested to have estrogenic, anti-estrogenic, or androgenic potential for relieving menopausal symptoms. We hypothesize that Avlimil could modulate the growth of estrogen receptor positive human breast cancer (MCF-7) cells in vitro and in vivo. A dimethylsulfoxide (DMSO) extract of Avlimil (0.001-100 mu g Avlimil powder equivalents/mL media) was tested for its estrogenic and anti-estrogenic effects on the growth of MCF-7 cells in vitro. We observed that the DMSO extract of Avlimil at low concentrations (0.1-50 mu g/mL media) dose-dependently increased MCF-7 cell proliferation in vitro, and Avlimil DMSO extract at 100 mu g/mL inhibited the growth of MCF-7 cells in vitro. Avlimil and some constituents (black cohosh and licorice roots) of Avlimil were fractionated by using sequential solvent extraction (hexane, ethyl acetate, and methanol) and the activities of the fractions were monitored by effects on the growth of MCF-7 cells. Depending on dosage (0.1-100 mu g/mL media) both stimulatory and inhibitory effects of the extracts on the growth of MCF-7 cells were observed. The effect of dietary Avlimil at dosages approximating human intake was evaluated using ovariectomized mice implanted with MCF-7 cells. Animals were fed diets containing 500 ppm or 1000 ppm Avlimil for 16 weeks. Dietary Avlimil at 500 ppm stimulated MCF-7 tumors, but Avlimil at 1000 ppm had no apparent effect on the growth of MCF-7 tumors. The observation of stimulated tumor growth in the absence of uterine wet weight gains suggest that estrogenic/anti-estrogenic effects of Avlimil we observed may be dosage-and target tissue-specific and that Avlimil may not be safe for women with estrogen-dependent breast cancer. The different biological effects of fractionated Avlimil components and the different concentration dependencies warrant further compound identification and dose-response studies, especially at recommended intake levels that could have estrogenic effects in women. (C) 2007 Published by Elsevier Ltd.