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. (c) 2004 Wiley-Liss, Inc.