{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T11:15:23Z","timestamp":1762254923483,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T00:00:00Z","timestamp":1718236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH National Institutes of Health (NIH) Director\u2019s Transformative Research Award","award":["R01-MD017405","1U54MD012392","U54MD007602"],"award-info":[{"award-number":["R01-MD017405","1U54MD012392","U54MD007602"]}]},{"name":"National Institute of Minority Health Disparities (NIMHD)","award":["R01-MD017405","1U54MD012392","U54MD007602"],"award-info":[{"award-number":["R01-MD017405","1U54MD012392","U54MD007602"]}]},{"name":"NIH National Center on Minority Health and Health Disparities","award":["R01-MD017405","1U54MD012392","U54MD007602"],"award-info":[{"award-number":["R01-MD017405","1U54MD012392","U54MD007602"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The G-protein-coupled estrogen receptor (GPER; G-protein-coupled estrogen receptor 30, also known as GPR30) is a novel estrogen receptor and has emerged as a promising target for ovarian cancer. GPER, a seven-transmembrane receptor, suppresses cellular viability and migration in studied ovarian cancer cells. However, its impact on the fallopian tube, which is the potential origin of high-grade serous (HGSC) ovarian cancer, has not been addressed. This study was conducted to evaluate the relationship of GPER, ovarian cancer subtypes, i.e., high-grade serous cell lines (OV90 and OVCAR420), as well as the cell type that is the potential origin of HGSC ovarian cancer (i.e., the fallopian tube cell line FT190). The selective ligand assessed here is the agonist G-1, which was utilized in an in vitro study to characterize its effects on cellular viability and migration. As a result, this study has addressed the effect of a specific GPER agonist on cell viability, providing a better understanding of the effects of this compound on our diverse group of studied cell lines. Strikingly, attenuated cell proliferation and migration behaviors were observed in the presence of G-1. Thus, our in vitro study reveals the impact of the origin of HGSC ovarian cancers and highlights the GPER agonist G-1 as a potential therapy for ovarian cancer.<\/jats:p>","DOI":"10.3390\/ijms25126499","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T03:52:53Z","timestamp":1718337173000},"page":"6499","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The G-Protein-Coupled Estrogen Receptor Selective Agonist G-1 Attenuates Cell Viability and Migration in High-Grade Serous Ovarian Cancer Cell Lines"],"prefix":"10.3390","volume":"25","author":[{"given":"Donia","family":"Hanafi","sequence":"first","affiliation":[{"name":"Julius L. Chambers Biomedical\/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA"},{"name":"Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8568-1575","authenticated-orcid":false,"given":"Rob U.","family":"Onyenwoke","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USA"},{"name":"Biomanufacturing Research Institute and Technology Enterprise (BRITE), North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2886-6124","authenticated-orcid":false,"given":"K. Sean","family":"Kimbro","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical\/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA"},{"name":"Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USA"},{"name":"Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine (MSM), Atlanta, GA 30310, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/canjclin.50.1.7","article-title":"Cancer statistics, 2000","volume":"50","author":"Greenlee","year":"2000","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1097\/00001622-199309000-00020","article-title":"The biology of ovarian cancer","volume":"5","author":"Boente","year":"1993","journal-title":"Curr. Opin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3080","DOI":"10.1002\/cncr.34350","article-title":"Real-life data on treatment and outcomes in advanced ovarian cancer: An observational, multinational cohort study (RESPONSE trial)","volume":"128","author":"Marth","year":"2022","journal-title":"Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1158\/0008-5472.CAN-06-2909","article-title":"G protein-coupled receptor 30 (GPR30) mediates gene expression changes and growth response to 17beta-estradiol and selective GPR30 ligand G-1 in ovarian cancer cells","volume":"67","author":"Albanito","year":"2007","journal-title":"Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/1757-2215-6-51","article-title":"GPER-1 acts as a tumor suppressor in ovarian cancer","volume":"6","author":"Ignatov","year":"2013","journal-title":"J. Ovarian Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jsbmb.2017.02.012","article-title":"Roles of G protein-coupled estrogen receptor GPER in metabolic regulation","volume":"176","author":"Sharma","year":"2018","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1172\/JCI27987","article-title":"Estrogen receptors and human disease","volume":"116","author":"Deroo","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/nrendo.2011.122","article-title":"The G-protein-coupled estrogen receptor GPER in health and disease","volume":"7","author":"Prossnitz","year":"2011","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e869","DOI":"10.1038\/cddis.2013.397","article-title":"The G-protein-coupled estrogen receptor agonist G-1 suppresses proliferation of ovarian cancer cells by blocking tubulin polymerization","volume":"4","author":"Wang","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nchembio775","article-title":"Virtual and biomolecular screening converge on a selective agonist for GPR30","volume":"2","author":"Bologa","year":"2006","journal-title":"Nat. Chem. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/nchembio.168","article-title":"In vivo effects of a GPR30 antagonist","volume":"5","author":"Dennis","year":"2009","journal-title":"Nat. Chem. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.jsbmb.2011.07.002","article-title":"Identification of a GPER\/GPR30 antagonist with improved estrogen receptor counterselectivity","volume":"127","author":"Dennis","year":"2011","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Vo, D.H., Hartig, R., Weinert, S., Haybaeck, J., and Nass, N. (2019). G-Protein-Coupled Estrogen Receptor (GPER)-Specific Agonist G1 Induces ER Stress Leading to Cell Death in MCF-7 Cells. Biomolecules, 9.","DOI":"10.3390\/biom9090503"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1007\/s00432-020-03333-4","article-title":"G protein-coupled estrogen receptor 1 (GPER-1) and agonist G-1 inhibit growth of ovarian cancer cells by activation of anti-tumoral transcriptome responses: Impact of GPER-1 mRNA on survival","volume":"146","author":"Skrzypczak","year":"2020","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Han, N., Heublein, S., Jeschke, U., Kuhn, C., Hester, A., Czogalla, B., Mahner, S., Rottmann, M., Mayr, D., and Schmoeckel, E. (2021). The G-Protein-Coupled Estrogen Receptor (GPER) Regulates Trimethylation of Histone H3 at Lysine 4 and Represses Migration and Proliferation of Ovarian Cancer Cells In Vitro. Cells, 10.","DOI":"10.3390\/cells10030619"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10799","DOI":"10.1038\/s41598-020-67533-1","article-title":"Identification of ovarian high-grade serous carcinoma cell lines that show estrogen-sensitive growth as xenografts in immunocompromised mice","volume":"10","author":"Box","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1158\/1535-7163.MCT-16-0626","article-title":"G-1 Inhibits Breast Cancer Cell Growth via Targeting Colchicine-Binding Site of Tubulin to Interfere with Microtubule Assembly","volume":"16","author":"Lv","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s12935-015-0263-4","article-title":"High-grade serous ovarian cancer cell lines exhibit heterogeneous responses to growth factor stimulation","volume":"15","author":"Bourgeois","year":"2015","journal-title":"Cancer Cell Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7864","DOI":"10.12659\/MSM.917735","article-title":"Antiproliferative Activity of Carnosic Acid is Mediated via Inhibition of Cell Migration and Invasion, and Suppression of Phosphatidylinositol 3-Kinases (PI3K)\/AKT\/Mammalian Target of Rapamycin (mTOR) Signaling Pathway","volume":"25","author":"Zhao","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4913","DOI":"10.21873\/anticanres.14494","article-title":"New Imidazo [2,1-b][1,3,4]Thiadiazole Derivatives Inhibit FAK Phosphorylation and Potentiate the Antiproliferative Effects of Gemcitabine Through Modulation of the Human Equilibrative Nucleoside Transporter-1 in Peritoneal Mesothelioma","volume":"40","author":"Pecoraro","year":"2020","journal-title":"Anticancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1038\/ncomms3126","article-title":"Evaluating cell lines as tumor models by comparison of genomic profiles","volume":"4","author":"Domcke","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.ygyno.2011.11.019","article-title":"RhoB mediates antitumor synergy of combined ixabepilone and sunitinib in human ovarian serous cancer","volume":"124","author":"Vishnu","year":"2012","journal-title":"Gynecol. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"W216","DOI":"10.1093\/nar\/gkab225","article-title":"Expasy, the Swiss Bioinformatics Resource Portal, as designed by its users","volume":"49","author":"Duvaud","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4599","DOI":"10.7314\/APJCP.2013.14.8.4599","article-title":"Curcumin inhibits human non-small cell lung cancer A549 cell proliferation through regulation of Bcl-2\/Bax and cytochrome C","volume":"14","author":"Li","year":"2013","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_25","first-page":"48","article-title":"Assessment of Cytotoxicity of Dimethyl Sulfoxide in Human Hematopoietic Tumor Cell Lines","volume":"9","author":"Hajighasemi","year":"2017","journal-title":"Iran. J. Blood Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.molonc.2016.01.002","article-title":"Activation of GPER suppresses epithelial mesenchymal transition of triple negative breast cancer cells via NF-\u03baB signals","volume":"10","author":"Chen","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1038\/cdd.2010.20","article-title":"Activation of GPR30 inhibits the growth of prostate cancer cells through sustained activation of Erk1\/2, c-jun\/c-fos-dependent upregulation of p21, and induction of G2 cell-cycle arrest","volume":"17","author":"Chan","year":"2010","journal-title":"Cell Death Differ."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12943-017-0654-3","article-title":"Epigenetic down regulation of G protein-coupled estrogen receptor (GPER) functions as a tumor suppressor in colorectal cancer","volume":"16","author":"Liu","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_29","first-page":"390","article-title":"The putative G-protein coupled estrogen receptor agonist G-1 suppresses proliferation of ovarian and breast cancer cells in a GPER-independent manner","volume":"4","author":"Wang","year":"2012","journal-title":"Am. J. Transl. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1002\/cbf.3154","article-title":"Role of GPER on proliferation, migration and invasion in ligand-independent manner in human ovarian cancer cell line SKOV3","volume":"33","author":"Yan","year":"2015","journal-title":"Cell Biochem. Funct."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11010-013-1579-9","article-title":"The novel estrogen receptor GPER regulates the migration and invasion of ovarian cancer cells","volume":"378","author":"Yan","year":"2013","journal-title":"Mol. Cell. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Lau, K.-M., and To, K.-F. (2016). Importance of Estrogenic Signaling and Its Mediated Receptors in Prostate Cancer. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091434"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1038\/s41467-020-15089-z","article-title":"Why the dual origins of high grade serous ovarian cancer matter","volume":"11","author":"Colvin","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.3390\/nu6041618","article-title":"Selected Activities of Citrus Maxima Merr. Fruits on Human Endothelial Cells: Enhancing Cell Migration and Delaying Cellular Aging","volume":"6","author":"Buachan","year":"2014","journal-title":"Nutrients"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/12\/6499\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:57:42Z","timestamp":1760108262000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/12\/6499"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,13]]},"references-count":34,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["ijms25126499"],"URL":"https:\/\/doi.org\/10.3390\/ijms25126499","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,6,13]]}}}