p38 Mitogen-activated protein kinases is required for counteraction of 2-methoxyestradiol to estradiol-stimulated cell proliferation and induction of apoptosis in ovarian carcinoma cells via phosphorylation Bcl-2

Apoptosis : an International Journal on Programmed Cell Death
S Z BuS S Zheng

Abstract

2-Methoxyestradiol (2ME2), a natural endogenous product of estradiol (E2) metabolism, has been shown to be a selective apoptotic agent for cancer cells but not for normal cells. In this study, we determined that 2ME2 counteracts E2-stimulated cell growth and induces apoptosis in ovarian carcinoma cells. In addition, we demonstrate that 2ME2 induces apoptosis via p38 and phospho-Bcl2 pathway. 2ME2 and/or E2 were administered to the OVCAR-3 (human ovarian cancer) cell line. Cell growth inhibition was analyzed by [3H] Thymidine incorporation assay and DNA fluorometric assay. Cell apoptosis was tested by DNA fragmentation analysis and FACS. The signaling pathway was determined by a series of biochemical assays. 2ME2 inhibited estradiol-stimulated cell growth and induced apoptosis in an ovarian carcinoma cell line. MAPK and p38, but not JNK, were found to be critical mediators in this process. Expression of a dominant negative mutant of p38 kinase or p38 specific inhibitor, SB 203580, almost completely blocked the process. Furthermore, Bcl-2 phosphorylation was required for 2ME2-induced effects. Our data suggest that 2ME2 inhibits E2-stimulated proliferation and induces apoptosis in ovarian carcinoma cells. Furthermore, activation o...Continue Reading

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Citations

Dec 26, 2008·Biology of Reproduction·Yue JiaAmiya P Sinha-Hikim
Sep 29, 2012·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Yinghui ChenGuoxiong Xu
Apr 26, 2014·Hormones & Cancer·Mauricio P PintoGareth I Owen
Nov 7, 2015·The Journal of Endocrinology·Christopher Price
May 27, 2008·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Eun-Sun Hwang, Hyong Joo Lee
Jun 4, 2008·Molecular Carcinogenesis·Masayuki Fukui, Bao Ting Zhu
Nov 21, 2014·Biology of Reproduction·Valério M PortelaChristopher A Price
Mar 27, 2007·Journal of Bacteriology·Sangita PhadtareKonstantin Severinov

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