G protein-coupled estrogen receptor 1 agonist G-1 induces cell cycle arrest in the mitotic phase, leading to apoptosis in endometriosis

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Abstract

Objective To demonstrate the effects of the selective G protein-coupled estrogen receptor 1 (GPER) agonist G-1 in human ovarian endometriotic stromal cells (ESCs). Design Experimental in vitro study. Setting University hospital. Patient(s) A total of 33 patients with ovarian endometrioma. Intervention(s) Endometriotic stromal cells from ovarian chocolate cysts were treated with the GPER agonist G-1. Main Outcome Measure(s) The primary outcomes were cell proliferation, measured using the WST-8 assay; cell cycle, as analyzed using flow cytometry, fluorescent immunocytochemistry, and cytotoxicity; caspase activity, as measured by fluorescent and luminescent enzyme assays; and protein expression levels, as determined by Western blot analysis. Result(s) G-1 suppressed ESC proliferation in a concentration-dependent manner. The inhibitory effect was not blocked when GPER signaling pathways, including the GPER itself, were inhibited. G-1 induced cell cycle arrest and accumulation in the sub-G<inf>1</inf> phase in ESCs. Immunofluorescence analysis demonstrated that G-1 interrupted microtubule assembly at the mitotic phase. G-1 also induced caspase-3-dependent apoptosis without significant cytotoxicity. Conclusion(s) G-1 suppressed proliferation and induced apoptosis in ESCs, suggesting the potential use of this compound as a therapeutic drug for the treatment of endometriosis.

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Mori, T., Ito, F., Matsushima, H., Takaoka, O., Tanaka, Y., Koshiba, A., … Kitawaki, J. (2015). G protein-coupled estrogen receptor 1 agonist G-1 induces cell cycle arrest in the mitotic phase, leading to apoptosis in endometriosis. Fertility and Sterility, 103(5), 1228-1235.e1. https://doi.org/10.1016/j.fertnstert.2015.01.026

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