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In vitro and in vivo antitumor effect of 2‐methoxyestradiol on human melanoma
Author(s) -
Dobos Judit,
Tímár József,
Bocsi József,
Burián Zsuzsanna,
Nagy Katalin,
Barna Gábor,
Peták István,
Ladányi Andrea
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20473
Subject(s) - 2 methoxyestradiol , melanoma , in vivo , apoptosis , cancer research , cell growth , in vitro , endogeny , mechanism of action , cell cycle checkpoint , biology , metabolite , estrogen , cell culture , pharmacology , cell cycle , endocrinology , biochemistry , genetics , microbiology and biotechnology
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.