Effect of 2‑methoxyestradiol on SK‑LMS‑1 uterine leiomyosarcoma cells

Lee,Ji‑Sun; Ahn,Changhwan; Kang,Hee Young; Jeung,Eui‑Bae

doi:10.3892/ol.2017.6165

Effect of 2‑methoxyestradiol on SK‑LMS‑1 uterine leiomyosarcoma cells

Authors:
- Ji‑Sun Lee
- Changhwan Ahn
- Hee Young Kang
- Eui‑Bae Jeung
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Affiliations: Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea
Published online on: May 12, 2017 https://doi.org/10.3892/ol.2017.6165
Pages: 103-110
Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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