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Effect of 2-methoxyestradiol on SK-LMS-1 uterine leiomyosarcoma cells.

ABSTRACT: An endogenous metabolite of 17β-estradiol, 2-methoxyestradiol (2-ME), has affinity for estrogen receptors. This compound was reported to be a promising antitumor drug due to its anti-proliferative effects on a wide range of tumor cell types. Numerous previous studies have been performed to evaluate the cytotoxic effects of 2-ME on tumor cell lines in following the induction of G2/M cell cycle arrest and subsequent apoptosis. Uterine leiomyosarcoma (ULMS) is a relatively rare malignant smooth muscle cell tumor that develops in the uterus muscle layer. The aim of the present study was to examine the in vitro anti-proliferative effects of 2-ME on SK-LMS-1 human leiomyosarcoma cells. An MTT assay, terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay, immunocytochemistry and western blotting were performed. A high concentration (10-5 M) of 2-ME was identified to have an anti-proliferative effect on SK-LMS-1 cells. Additionally, expression of the apoptosis markers was upregulated in the presence of 10-5 M 2-ME, according to western blot analysis. Furthermore, the expression level of an autophagic marker, light chain 3, was increased by 2-ME treatment in a dose-dependent manner. This was associated with cell death induced by the upregulation of phosphorylated extracellular-signal-regulated kinase 1/2 signaling pathway. The results of the present study demonstrated that 2-ME, which is used as a therapeutic agent for treating solid tumors, exhibits apoptotic and anti-proliferative effects depending on the dose. Therefore, 2-ME may be a potential therapeutic reagent for human ULMS, but the appropriate dose of this compound should be carefully selected.

SUBMITTER: Lee JS

PROVIDER: S-EPMC5494911 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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