2-methoxyestradiol inhibits differentiation and is cytotoxic to osteoclasts

Journal of Cellular Biochemistry
Avudaiappan MaranRussell T Turner

Abstract

2-Methoxyestradiol (2-ME), a naturally occurring metabolite of 17beta-estradiol, is highly cytotoxic to a wide range of tumor cells but is harmless to most normal cells. However, 2-ME prevented bone loss in ovariectomized rats, suggesting it inhibits bone resorption. These studies were performed to determine the direct effects of 2-ME on cultured osteoclasts. 2-ME (2 microM) reduced osteoclast number by more than 95% and induced apoptosis in three cultured osteoclast model systems (RAW 264.7 cells cultured with RANKL, marrow cells co-cultured with stromal support cells, and spleen cells cultured without support cells in media supplemented with RANKL and macrophage colony stimulating factor (M-CSF)). The 2-ME-mediated effect was ligand specific; 2-hydroxyestradiol (2-OHE), the immediate precursor to 2-ME, exhibited less cytotoxicity; and 2-methoxyestrone (2-MEOE1) the estrone analog of 2-ME, was not cytotoxic. Co-treatment with ICI 182,780 did not antagonize 2-ME, suggesting that the cytotoxicity was not estrogen receptor-dependent. 2-ME-induced cell death in RAW 264.7 cells coincided with an increase in gene expression of cytokines implicated in inhibition of differentiation and induction of apoptosis. In addition, the 2-ME-med...Continue Reading

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Citations

Apr 5, 2011·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Alexandra StubeliusHans Carlsten
Jan 29, 2013·Journal of Biomedical Materials Research. Part a·Avudaiappan MaranMichael J Yaszemski
Jan 19, 2010·Journal of Cellular Biochemistry·Michaela B BenediktAvudaiappan Maran
Nov 20, 2018·Reproduction, Fertility, and Development·Emanuel Guajardo-CorreaPedro A Orihuela
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Nov 3, 2007·Cancer Research·Muzaffer CicekMerry Jo Oursler
Nov 24, 2020·Frontiers in Oncology·Kelechi NjokuEmma J Crosbie

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