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.


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



To demonstrate the effects of the selective G protein–coupled estrogen receptor 1 (GPER) agonist G-1 in human ovarian endometriotic stromal cells (ESCs).


Experimental in vitro study.


University hospital.


A total of 33 patients with ovarian endometrioma.


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.


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.


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