Orally administered endoxifen inhibits tumor growth in melanoma-bearing mice.

Endoxifen, an active metabolite of tamoxifen, has been shown to be an effective anti-estrogenic agent in estrogen receptor-positive breast cancer patients. In melanoma, estrogen receptor expression is shown to be associated with disease progression. However, the therapeutic benefit of endoxifen in melanoma has not yet been evaluated. Here, we present the first demonstration of the anti-melanogenic activity of endoxifen in vitro and in vivo. The in vitro cytotoxic effect of endoxifen was tested using a cell viability assay. The in vivo anti-melanogenic activity was evaluated in B16F10 cell-bearing C57BL/6 mice, a mouse melanoma model. The general toxicity was tested in Swiss albino mice. Endoxifen exhibited greater activity against melanoma cell lines. Treatment of B16F10 mouse and SK-MEL-5 human melanoma cell lines with 10 μM of endoxifen for 48 h respectively resulted in 93.6 and 92.5% cell death. Orally administered endoxifen, at dose levels of 4 and 8 mg/kg body weight/day for 20 consecutive days, respectively reduced metastatic melanoma nodules in the lungs by 26.7 and 82.7%. Endoxifen was found to be a safe and effective anti-melanogenic agent in animal studies.