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

G-1 induces cell cycle arrest and apoptosis in ovarian endometriotic stromal cells in a G protein– coupled estrogen receptor 1–independent manner, suggesting its potential as a therapeutic drug for endometriosis.

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Authors

Taisuke Mori, M.D., Ph.D., Fumitake Ito, M.D., Hiroshi Matsushima, M.D., Osamu Takaoka, M.D., Yukiko Tanaka, M.D., Akemi Koshiba, M.D., Izumi Kusuki, M.D., Ph.D., Jo Kitawaki, M.D., Ph.D.

Volume 103, Issue 5, Pages 1228-1235

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-G1 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.

Read the full text at: http://www.fertstert.org/article/S0015-0282(15)00073-4/fulltext


Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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