| AJTR Copyright © 2009-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Am J Transl Res 2012;4(4):390-402
Original Article
The putative G-protein coupled estrogen receptor agonist G-1
suppresses proliferation of ovarian and breast cancer cells in a GPER-
independent manner
Cheng Wang, Xiangmin Lv, Chao Jiang, John S Davis
Olson Center for Women’s Health, Department of OB/GYN, University of Nebraska Medical Center, Omaha, NE
68198, USA; VA Medical Center, Omaha, NE 68105, USA; Key Laboratory of Protein Chemistry and
Developmental Biology of Education Ministry of China, College of Life Sciences, Hunan Normal University,
Changsha, Hunan 410081, China.
Received July 17, 2012; accepted September 19, 2012; Epub October 10, 2012; Published October 30, 2012
Abstract: G-protein coupled estrogen receptor 1 (GPER) plays an important role in mediating estrogen action in
many different tissues under both physiological and pathological conditions. G-1 (1-[4-(6-bromobenzo[1,3]dioxol-
5yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta [c]quinolin-8-yl]-ethanone) has been developed as a selective GPER
agonist to distinguish estrogen actions mediated by GPER from those mediated by classic estrogen receptors. In
the present study, we surprisingly found that G-1 suppressed proliferation and induced apoptosis of KGN cells (a
human ovarian granulosa cell tumor cell line), actions that were not blocked by a selective GPER antagonist G15
or siRNA knockdown of GPER. G-1 also suppressed proliferation and induced cell apoptosis in GPER-negative
HEK-293 cells and MDA-MB 231 breast cancer cells. Our results demonstrate that G-1 suppresses proliferation
of ovarian and breast cancer cells in a GPER-independent manner. G-1 may be a candidate for the development
of drugs against ovarian and breast cancer. (AJTR1207005).
Keywords: GPR30/GPER, G-1, G15, ovarian cancer, breast cancer, estrogen receptors
Address all correspondence to:
Dr. John S Davis, Olson Center for Women’s Health, Department of Obstetrics and Gynecology, University of
Nebraska Medical Center, Omaha NE 68198-6265. Tel: 402-559-9079; Fax: 402-559-5015; E-mail:
jsdavis@unmc.edu. Dr. Cheng Wang, Olson Center for Women’s Health, Department of Obstetrics and
Gynecology, University of Nebraska Medical Center, Omaha NE 68198-6265. Tel: 402-559-8665; Fax: 402-559-
6164; E-mail: chengwang@unmc.edu
Original Article
The putative G-protein coupled estrogen receptor agonist G-1
suppresses proliferation of ovarian and breast cancer cells in a GPER-
independent manner
Cheng Wang, Xiangmin Lv, Chao Jiang, John S Davis
Olson Center for Women’s Health, Department of OB/GYN, University of Nebraska Medical Center, Omaha, NE
68198, USA; VA Medical Center, Omaha, NE 68105, USA; Key Laboratory of Protein Chemistry and
Developmental Biology of Education Ministry of China, College of Life Sciences, Hunan Normal University,
Changsha, Hunan 410081, China.
Received July 17, 2012; accepted September 19, 2012; Epub October 10, 2012; Published October 30, 2012
Abstract: G-protein coupled estrogen receptor 1 (GPER) plays an important role in mediating estrogen action in
many different tissues under both physiological and pathological conditions. G-1 (1-[4-(6-bromobenzo[1,3]dioxol-
5yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta [c]quinolin-8-yl]-ethanone) has been developed as a selective GPER
agonist to distinguish estrogen actions mediated by GPER from those mediated by classic estrogen receptors. In
the present study, we surprisingly found that G-1 suppressed proliferation and induced apoptosis of KGN cells (a
human ovarian granulosa cell tumor cell line), actions that were not blocked by a selective GPER antagonist G15
or siRNA knockdown of GPER. G-1 also suppressed proliferation and induced cell apoptosis in GPER-negative
HEK-293 cells and MDA-MB 231 breast cancer cells. Our results demonstrate that G-1 suppresses proliferation
of ovarian and breast cancer cells in a GPER-independent manner. G-1 may be a candidate for the development
of drugs against ovarian and breast cancer. (AJTR1207005).
Keywords: GPR30/GPER, G-1, G15, ovarian cancer, breast cancer, estrogen receptors
Address all correspondence to:
Dr. John S Davis, Olson Center for Women’s Health, Department of Obstetrics and Gynecology, University of
Nebraska Medical Center, Omaha NE 68198-6265. Tel: 402-559-9079; Fax: 402-559-5015; E-mail:
jsdavis@unmc.edu. Dr. Cheng Wang, Olson Center for Women’s Health, Department of Obstetrics and
Gynecology, University of Nebraska Medical Center, Omaha NE 68198-6265. Tel: 402-559-8665; Fax: 402-559-
6164; E-mail: chengwang@unmc.edu
 | |  | |  | |  | |  | |  | |  |