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


METHODS
Experimental in vitro study.


METHODS
University hospital.


METHODS
A total of 33 patients with ovarian endometrioma.


METHODS
Endometriotic stromal cells from ovarian chocolate cysts were treated with the GPER agonist G-1.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: moriman@koto.kpu-m.ac.jp.
Taisuke
T
Mori
Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Fumitake
F
Ito
Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Hiroshi
H
Matsushima
Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Osamu
O
Takaoka
Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yukiko
Y
Tanaka
Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Akemi
A
Koshiba
Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Izumi
I
Kusuki
Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Jo
J
Kitawaki
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003517:Cyclopentanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D010048:Ovarian Cysts / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011804:Quinolines / Q000494:pharmacology*; D034622:RNA Interference; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014162:Transfection
C517943:1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone; D003517:Cyclopentanes; C109584:GPER1 protein, human; D011804:Quinolines; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C505407:CASP3 protein, human; D053148:Caspase 3
G-1; GPER; apoptosis; cell cycle arrest; endometriosis