In vitro and in vivo antitumor effect of 2‐methoxyestradiol on human melanoma

2‐methoxyestradiol (2ME 2 ) is an endogenous metabolite of estradiol with estrogen‐receptor‐independent antitumor and antiangiogenic activity. We examined the effects of 2ME 2 on the cellular proliferation of 8 human melanoma cell lines. We show that 2ME 2 inhibited cell proliferation by inducing apoptosis and an arrest in the G 2 /M phase, and the mechanism of action involved microtubules, mitochondrial damage and caspase activation. In male SCID mice, 2ME 2 was effective in reducing primary tumor weight and the number of liver metastases after intrasplenic injection of human melanoma cells. In the metastases, we found a significantly higher rate of apoptotic cells after 2ME 2 treatment. These findings on the antitumor effect of 2ME 2 in cell culture as well as in an animal model may have implications for designing alternative treatment options for patients with advanced malignant melanoma. © 2004 Wiley‐Liss, Inc.