The G-Protein-Coupled Estrogen Receptor Selective Agonist G-1 Attenuates Cell Viability and Migration in High-Grade Serous Ovarian Cancer Cell Lines
Abstract
:1. Introduction
2. Results
2.1. Effect of DMSO Concentrations on Cell Viability
2.2. Inhibitory Effect of the G-1 Agonist on Cell Viability
2.3. Inhibitory Effect of G-1 Agonist on Cell Migration
3. Discussion
4. Methods and Materials
4.1. Cell Culture and Reagents
4.2. Cell Viability Assay
4.3. Migration Assay (Also Known as a “Wound Healing Assay”)
4.4. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Greenlee, R.T.; Murray, T.; Bolden, S.; Wingo, P.A. Cancer statistics, 2000. CA Cancer J. Clin. 2000, 50, 7–33. [Google Scholar] [CrossRef] [PubMed]
- Boente, M.P.; Hurteau, J.; Rodriguez, G.C.; Bast, R.C., Jr.; Berchuck, A. The biology of ovarian cancer. Curr. Opin. Oncol. 1993, 5, 900–907. [Google Scholar] [CrossRef] [PubMed]
- Marth, C.; Abreu, M.H.; Andersen, K.K.; Aro, K.M.; de Lurdes Batarda, M.; Boll, D.; Ekmann-Gade, A.W.; Haltia, U.M.; Hansen, J.; Haug, A.J.; et al. Real-life data on treatment and outcomes in advanced ovarian cancer: An observational, multinational cohort study (RESPONSE trial). Cancer 2022, 128, 3080–3089. [Google Scholar] [CrossRef] [PubMed]
- Albanito, L.; Madeo, A.; Lappano, R.; Vivacqua, A.; Rago, V.; Carpino, A.; Oprea, T.I.; Prossnitz, E.R.; Musti, A.M.; Andò, S.; et al. 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. Cancer Res. 2007, 67, 1859–1866. [Google Scholar] [CrossRef] [PubMed]
- Ignatov, T.; Modl, S.; Thulig, M.; Weißenborn, C.; Treeck, O.; Ortmann, O.; Zenclussen, A.C.; Costa, S.D.; Kalinski, T.; Ignatov, A. GPER-1 acts as a tumor suppressor in ovarian cancer. J. Ovarian Res. 2013, 6, 51. [Google Scholar] [CrossRef] [PubMed]
- Sharma, G.; Mauvais-Jarvis, F.; Prossnitz, E.R. Roles of G protein-coupled estrogen receptor GPER in metabolic regulation. J. Steroid Biochem. Mol. Biol. 2018, 176, 31–37. [Google Scholar] [CrossRef] [PubMed]
- Deroo, B.J.; Korach, K.S. Estrogen receptors and human disease. J. Clin. Investig. 2006, 116, 561–570. [Google Scholar] [CrossRef] [PubMed]
- Prossnitz, E.R.; Barton, M. The G-protein-coupled estrogen receptor GPER in health and disease. Nat. Rev. Endocrinol. 2011, 7, 715–726. [Google Scholar] [CrossRef]
- Wang, C.; Lv, X.; He, C.; Hua, G.; Tsai, M.Y.; Davis, J.S. The G-protein-coupled estrogen receptor agonist G-1 suppresses proliferation of ovarian cancer cells by blocking tubulin polymerization. Cell Death Dis. 2013, 4, e869. [Google Scholar] [CrossRef]
- Bologa, C.G.; Revankar, C.M.; Young, S.M.; Edwards, B.S.; Arterburn, J.B.; Kiselyov, A.S.; Parker, M.A.; Tkachenko, S.E.; Savchuck, N.P.; Sklar, L.A.; et al. Virtual and biomolecular screening converge on a selective agonist for GPR30. Nat. Chem. Biol. 2006, 2, 207–212. [Google Scholar] [CrossRef]
- Dennis, M.K.; Burai, R.; Ramesh, C.; Petrie, W.K.; Alcon, S.N.; Nayak, T.K.; Bologa, C.G.; Leitao, A.; Brailoiu, E.; Deliu, E.; et al. In vivo effects of a GPR30 antagonist. Nat. Chem. Biol. 2009, 5, 421–427. [Google Scholar] [CrossRef] [PubMed]
- Dennis, M.K.; Field, A.S.; Burai, R.; Ramesh, C.; Petrie, W.K.; Bologa, C.G.; Oprea, T.I.; Yamaguchi, Y.; Hayashi, S.-I.; Sklar, L.A.; et al. Identification of a GPER/GPR30 antagonist with improved estrogen receptor counterselectivity. J. Steroid Biochem. Mol. Biol. 2011, 127, 358–366. [Google Scholar] [CrossRef] [PubMed]
- Vo, D.H.; Hartig, R.; Weinert, S.; Haybaeck, J.; Nass, N. G-Protein-Coupled Estrogen Receptor (GPER)-Specific Agonist G1 Induces ER Stress Leading to Cell Death in MCF-7 Cells. Biomolecules 2019, 9, 503. [Google Scholar] [CrossRef] [PubMed]
- Schuler-Toprak, S.; Skrzypczak, M.; Ignatov, T.; Ignatov, A.; Ortmann, O.; Treeck, O. 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. J. Cancer Res. Clin. Oncol. 2020, 146, 3175–3188. [Google Scholar] [CrossRef] [PubMed]
- Han, N.; Heublein, S.; Jeschke, U.; Kuhn, C.; Hester, A.; Czogalla, B.; Mahner, S.; Rottmann, M.; Mayr, D.; Schmoeckel, E.; et al. 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 2021, 10, 619. [Google Scholar] [CrossRef] [PubMed]
- De Haven Brandon, A.; Box, G.; Hallsworth, A.; Court, W.; Matthews, N.; Herodek, B.; Arteagabeitia, A.B.; Valenti, M.; Kirkin, V. Identification of ovarian high-grade serous carcinoma cell lines that show estrogen-sensitive growth as xenografts in immunocompromised mice. Sci. Rep. 2020, 10, 10799. [Google Scholar] [CrossRef] [PubMed]
- Lv, X.; He, C.; Huang, C.; Hua, G.; Wang, Z.; Remmenga, S.W.; Rodabough, K.J.; Karpf, A.R.; Dong, J.; Davis, J.S.; et al. G-1 Inhibits Breast Cancer Cell Growth via Targeting Colchicine-Binding Site of Tubulin to Interfere with Microtubule Assembly. Mol. Cancer Ther. 2017, 16, 1080–1091. [Google Scholar] [CrossRef] [PubMed]
- Bourgeois, D.L.; Kabarowski, K.A.; Porubsky, V.L.; Kreeger, P.K. High-grade serous ovarian cancer cell lines exhibit heterogeneous responses to growth factor stimulation. Cancer Cell Int. 2015, 15, 112. [Google Scholar] [CrossRef] [PubMed]
- Zhao, L.; Zhang, J.; Fan, Y.; Li, Y. 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. Med. Sci. Monit. 2019, 25, 7864–7871. [Google Scholar] [CrossRef]
- Li Petri, G.; Pecoraro, C.; Randazzo, O.; Zoppi, S.; Cascioferro, S.M.; Parrino, B.; Carbone, D.; El Hassouni, B.; Cavazzoni, A.; Zaffaroni, N.; et al. 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. Anticancer Res. 2020, 40, 4913–4919. [Google Scholar] [CrossRef]
- Domcke, S.; Sinha, R.; Levine, D.; Sander, C.; Schultz, N. Evaluating cell lines as tumor models by comparison of genomic profiles. Nat. Commun. 2013, 4, 2126. [Google Scholar] [CrossRef] [PubMed]
- Vishnu, P.; Colon-Otero, G.; Kennedy, G.T.; Marlow, L.A.; Kennedy, W.P.; Wu, K.J.; Santoso, J.T.; Copland, J.A. RhoB mediates antitumor synergy of combined ixabepilone and sunitinib in human ovarian serous cancer. Gynecol. Oncol. 2012, 124, 589–597. [Google Scholar] [CrossRef] [PubMed]
- Duvaud, S.; Gabella, C.; Lisacek, F.; Stockinger, H.; Ioannidis, V.; Durinx, C. Expasy, the Swiss Bioinformatics Resource Portal, as designed by its users. Nucleic Acids Res. 2021, 49, W216–W227. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Zhang, S.; Geng, J.X.; Hu, X.Y. Curcumin inhibits human non-small cell lung cancer A549 cell proliferation through regulation of Bcl-2/Bax and cytochrome C. Asian Pac. J. Cancer Prev. 2013, 14, 4599–4602. [Google Scholar] [CrossRef] [PubMed]
- Hajighasemi, F.; Tajic, S. Assessment of Cytotoxicity of Dimethyl Sulfoxide in Human Hematopoietic Tumor Cell Lines. Iran. J. Blood Cancer 2017, 9, 48–53. [Google Scholar]
- Chen, Z.-J.; Wei, W.; Jiang, G.-M.; Liu, H.; Wei, W.-D.; Yang, X.; Wu, Y.-M.; Liu, H.; Wong, C.K.C.; Du, J.; et al. Activation of GPER suppresses epithelial mesenchymal transition of triple negative breast cancer cells via NF-κB signals. Mol. Oncol. 2016, 10, 775–788. [Google Scholar] [CrossRef] [PubMed]
- Chan, Q.K.Y.; Lam, H.M.; Ng, C.F.; Lee, A.Y.Y.; Chan, E.S.Y.; Ng, H.K.; Ho, S.M.; Lau, K.M. 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. Cell Death Differ. 2010, 17, 1511–1523. [Google Scholar] [CrossRef]
- Liu, Q.; Chen, Z.; Jiang, G.; Zhou, Y.; Yang, X.; Huang, H.; Liu, H.; Du, J.; Wang, H. Epigenetic down regulation of G protein-coupled estrogen receptor (GPER) functions as a tumor suppressor in colorectal cancer. Mol. Cancer 2017, 16, 87. [Google Scholar] [CrossRef]
- Wang, C.; Lv, X.; Jiang, C.; Davis, J.S. The putative G-protein coupled estrogen receptor agonist G-1 suppresses proliferation of ovarian and breast cancer cells in a GPER-independent manner. Am. J. Transl. Res. 2012, 4, 390. [Google Scholar]
- Yan, Y.; Jiang, X.; Zhao, Y.; Wen, H.; Liu, G. Role of GPER on proliferation, migration and invasion in ligand-independent manner in human ovarian cancer cell line SKOV3. Cell Biochem. Funct. 2015, 33, 552–559. [Google Scholar] [CrossRef]
- Yan, Y.; Liu, H.; Wen, H.; Jiang, X.; Cao, X.; Zhang, G.; Liu, G. The novel estrogen receptor GPER regulates the migration and invasion of ovarian cancer cells. Mol. Cell. Biochem. 2013, 378, 1–7. [Google Scholar] [CrossRef] [PubMed]
- Lau, K.-M.; To, K.-F. Importance of Estrogenic Signaling and Its Mediated Receptors in Prostate Cancer. Int. J. Mol. Sci. 2016, 17, 1434. [Google Scholar] [CrossRef] [PubMed]
- Colvin, E.K.; Howell, V.M. Why the dual origins of high grade serous ovarian cancer matter. Nat. Commun. 2020, 11, 1200. [Google Scholar] [CrossRef] [PubMed]
- Buachan, P.; Chularojmontri, L.; Wattanapitayakul, S. Selected Activities of Citrus Maxima Merr. Fruits on Human Endothelial Cells: Enhancing Cell Migration and Delaying Cellular Aging. Nutrients 2014, 6, 1618–1634. [Google Scholar] [CrossRef] [PubMed]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Hanafi, D.; Onyenwoke, R.U.; Kimbro, K.S. The G-Protein-Coupled Estrogen Receptor Selective Agonist G-1 Attenuates Cell Viability and Migration in High-Grade Serous Ovarian Cancer Cell Lines. Int. J. Mol. Sci. 2024, 25, 6499. https://doi.org/10.3390/ijms25126499
Hanafi D, Onyenwoke RU, Kimbro KS. The G-Protein-Coupled Estrogen Receptor Selective Agonist G-1 Attenuates Cell Viability and Migration in High-Grade Serous Ovarian Cancer Cell Lines. International Journal of Molecular Sciences. 2024; 25(12):6499. https://doi.org/10.3390/ijms25126499
Chicago/Turabian StyleHanafi, Donia, Rob U. Onyenwoke, and K. Sean Kimbro. 2024. "The G-Protein-Coupled Estrogen Receptor Selective Agonist G-1 Attenuates Cell Viability and Migration in High-Grade Serous Ovarian Cancer Cell Lines" International Journal of Molecular Sciences 25, no. 12: 6499. https://doi.org/10.3390/ijms25126499