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G-1 Inhibits Breast Cancer Cell Growth via Targeting Colchicine-Binding Site of Tubulin to Interfere with Microtubule Assembly
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Abstract
G-protein–coupled estrogen receptor 1 (GPER1) has been reported to play a significant role in mediating the rapid estrogen actions in a wide range of normal and cancer cells. G-1 was initially developed as a selective agonist for GPER. However, the molecular mechanisms underlying the actions of G-1 are unknown, and recent studies report inconsistent effects of G-1 on the growth of breast cancer cells. By employing high-resolution laser scanning confocal microscopy and time-lapse imaging technology, as well as biochemical analyses, in the current study, we provide convincing in vitro and in vivo evidence that G-1 is able to suppress the growth of breast cancer cells independent of the expression status of GPERs and classic estrogen receptors. Interestingly, we found that triple-negative breast cancer cells (TNBC) are very sensitive to G-1 treatment. We found that G-1 arrested the cell cycle in the prophase of mitosis, leading to caspase activation and apoptosis of breast cancer cells. Our mechanistic studies indicated that G-1, similar to colchicine and 2-methoxyestradiol, binds to colchicine binding site on tubulin, inhibiting tubulin polymerization and subsequent assembly of normal mitotic spindle apparatus during breast cancer cell mitosis. Therefore, G-1 is a novel microtubule-targeting agent and could be a promising anti-microtubule drug for breast cancer treatment, especially for TNBC treatment. Mol Cancer Ther; 16(6); 1080–91. ©2017 AACR.
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“Both fostamatinib and colchicine have shown antitumor and anti-metastasis effects in animal models of breast cancer34,35.”
From ASGARD is a single-cell guided pipeline to aid repurposing of drugs (2023) · cites this paper as [34]
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Cites
Jemal, A., Bray, F., Ferlay, J., Ward, E., & Forman, D. (2011) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20107 · Cited by 55,077
Microtubules as a target for anticancer drugs
Jordan, M. A., & Wilson, L. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1317 · Cited by 4,000
A transmembrane intracellular estrogen receptor mediates rapid cell signaling
Revankar, C. M., Cimino, D. F., Sklar, L. A., Arterburn, J. B., & Prossnitz, E. R. (2005) · Science · doi:10.1126/science.1106943 · Cited by 2,302
Caspase-3 Is Required for DNA Fragmentation and Morphological Changes Associated with Apoptosis
Jänicke, R. U., Sprengart, M. L., Wati, M. R., & Porter, A. G. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.16.9357 · Cited by 1,955
Estrogen Carcinogenesis in Breast Cancer
Yager, J. D., & Davidson, N. E. (2006) · New England Journal of Medicine · doi:10.1056/nejmra050776 · Cited by 1,890
Microtubule-binding agents: a dynamic field of cancer therapeutics
Dumontet, C., & Jordan, M. A. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3253 · Cited by 1,773
Identity of an Estrogen Membrane Receptor Coupled to a G Protein in Human Breast Cancer Cells
Thomas, P., Pang, Y., Filardo, E. J., & Dong, J. (2004) · Endocrinology · doi:10.1210/en.2004-1064 · Cited by 1,410
Self-citationThe G-protein-coupled estrogen receptor GPER in health and disease
Prossnitz, E. R., & Barton, M. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.122 · Cited by 925 · cited 2×
“Since its first report in 2006, G-1 has been wildly used to investigate the functions of GPER in various tissues and organs (4).”
BackgroundFilardo, E. J., Quinn, J. A., Frackelton, A. R., & Bland, K. I. (2002) · Molecular Endocrinology · doi:10.1210/mend.16.1.0758 · Cited by 907
Virtual and biomolecular screening converge on a selective agonist for GPR30
Bologa, C., Revankar, C. M., Young, S. M., Edwards, B. S., Arterburn, J. B., Kiselyov, A. S., Parker, M. A., Tkachenko, S. E., Savchuk, N., Sklar, L. A., et al. (2006) · Nature Chemical Biology · doi:10.1038/nchembio775 · Cited by 819
An overview of tubulin inhibitors that interact with the colchicine binding site
Lu, Y., Chen, J., Xiao, M., Li, W., & Miller, D. D. (2012) · Pharmaceutical Research · doi:10.1007/s11095-012-0828-z · Cited by 709
Carmeci, C., Thompson, D. A., Ring, H. Z., Francke, U., & Weigel, R. J. (1997) · Genomics · doi:10.1006/geno.1997.4972 · Cited by 590
In vivo effects of a GPR30 antagonist
Dennis, M. K., Burai, R., Ramesh, C., Petrie, W. K., Alcon, S. N., Nayak, T. K., Bologa, C., Leitão, A., Brailoiu, E., Deliu, E., et al. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.168 · Cited by 533
Maggiolini, M., Vivacqua, A., Fasanella, G., Recchia, A. G., Sisci, D., Pezzi, V., Montanaro, D., Musti, A. M., Picard, D., & Andò, S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403588200 · Cited by 448
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. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2909 · Cited by 399
Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF
Pandey, D. P., Lappano, R., Albanito, L., Madeo, A., Maggiolini, M., & Picard, D. (2009) · The EMBO Journal · doi:10.1038/emboj.2008.304 · Cited by 327
Identification of a GPER/GPR30 antagonist with improved estrogen receptor counterselectivity
Dennis, M. K., Field, A. S., Burai, R., Ramesh, C., Petrie, W. K., Bologa, C., Oprea, T. I., Yamaguchi, Y., Hayashi, S., Sklar, L. A., et al. (2011) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2011.07.002 · Cited by 312
He, C., Mao, D., Hua, G., Lv, X., Chen, X., Angeletti, P. C., Dong, J., Remmenga, S. W., Rodabaugh, K. J., Zhou, J. R., et al. (2015) · EMBO Molecular Medicine · doi:10.15252/emmm.201404976 · Cited by 290
Self-citationEstrogen receptors and human disease: an update
Burns, K. A., & Korach, K. (2012) · Archives of Toxicology · doi:10.1007/s00204-012-0868-5 · Cited by 287
Ariazi, E. A., Brailoiu, E., Yerrum, S., Shupp, H. A., Slifker, M. J., Cunliffe, H. E., Black, M. A., Donato, A. L., Arterburn, J. B., Oprea, T. I., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-3068 · Cited by 236
Chan, Q. K. Y., Lam, H. C. M., Ng, C., Lee, A., Chan, E. S. Y., Ng, H., Ho, S., & Lau, K.-M. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.20 · Cited by 211
G-protein-coupled estrogen receptor GPR30 and tamoxifen resistance in breast cancer
Ignatov, A., Ignatov, T., Weißenborn, C., Eggemann, H., Bischoff, J., Semczuk, A., Roessner, A., Costa, S. D., & Kalinski, T. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1584-1 · Cited by 172
2-Methoxyestradiol—Biology and mechanism of action
Mueck, A. O., & Seeger, H. (2010) · Steroids · doi:10.1016/j.steroids.2010.02.016 · Cited by 171
Role of GPR30 in the mechanisms of tamoxifen resistance in breast cancer MCF-7 cells
Ignatov, A., Ignatov, T., Roessner, A., Costa, S. D., & Kalinski, T. (2009) · Breast Cancer Research and Treatment · doi:10.1007/s10549-009-0624-6 · Cited by 168
He, Y., Cai, B., Yang, Y., Liu, X., & Wan, X. (2009) · Cancer Science · doi:10.1111/j.1349-7006.2009.01148.x · Cited by 158
Wu, W. D., Chen, Z.-J., Zhang, K.-S., Yang, X.-L., Wu, Y.-M., Chen, X.-H., Huang, H.-B., Liu, H.-L., Cai, S.-H., Du, J., et al. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.398 · Cited by 136
GPER Mediates Activation of HIF1α/VEGF Signaling by Estrogens
Francesco, E. M. D., PELLEGRINO, M. A., Santolla, M. F., Lappano, R., Ricchio, E., Abonante, S., & Maggiolini, M. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-3590 · Cited by 133
He, C., Lv, X., Hua, G., Lele, S. M., Remmenga, S. W., Dong, J., Davis, J. S., & Wang, C. (2015) · Oncogene · doi:10.1038/onc.2015.52 · Cited by 117
Self-citationScaling, A. L., Prossnitz, E. R., & Hathaway, H. J. (2014) · Hormones and Cancer · doi:10.1007/s12672-014-0174-1 · Cited by 111
YAP regulates cell proliferation, migration, and steroidogenesis in adult granulosa cell tumors
Fu, Z., Lv, X., Hua, G., He, C., Dong, J., Lele, S. M., Li, D. W.-C., Zhai, Q.-L., Davis, J. S., & Wang, C. (2014) · Endocrine Related Cancer · doi:10.1530/erc-13-0339 · Cited by 107
Self-citationChevalier, N., Vega, A., Bouskine, A., Siddeek, B., Michiels, J., Chevallier, D., & Fénichel, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034672 · Cited by 101
Wang, C., Lv, X., He, C., Hua, G., Tsai, M.-Y., & Davis, J. S. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.397 · Cited by 100
Self-citationGPER-1 acts as a tumor suppressor in ovarian cancer
Ignatov, T., Modl, S., Thulig, M., Weißenborn, C., Treeck, O., Ortmann, O., Zenclussen, A. C., Costa, S. D., Kalinski, T., & Ignatov, A. (2013) · Journal of Ovarian Research · doi:10.1186/1757-2215-6-51 · Cited by 98
Vivacqua, A., Romeo, E., Marco, P. D., Francesco, E. M. D., Abonante, S., & Maggiolini, M. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1901-8 · Cited by 96
SIRT1 is involved in oncogenic signaling mediated by GPER in breast cancer
Santolla, M. F., Avino, S., PELLEGRINO, M. A., Francesco, E. M. D., Marco, P. D., Lappano, R., Vivacqua, A., Cirillo, F., Rigiracciolo, D. C., Scarpelli, A., et al. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.201 · Cited by 92
YAP induces high-grade serous carcinoma in fallopian tube secretory epithelial cells
Hua, G., Lv, X., He, C., Remmenga, S. W., Rodabough, K. J., Dong, J., Yang, L., Lele, S. M., Yang, P., Zhou, J., et al. (2015) · Oncogene · doi:10.1038/onc.2015.288 · Cited by 83
Self-citationEstrogen receptors in resistance to hormone therapy.
Herynk, M. H., & Fuqua, S. (2007) · Advances in Experimental Medicine and Biology · doi:10.1007/978-0-387-74039-3_10 · Cited by 64
Wang, C., Lv, X., Jiang, C. Q., & Davis, J. S. (2012) · Europe PMC (PubMed Central) · Cited by 61
Self-citationGPER functions as a tumor suppressor in MCF-7 and SK-BR-3 breast cancer cells
Weißenborn, C., Ignatov, T., Poehlmann, A., et al. (2014) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-014-1598-2 · Cited by 60
GPER agonist G-1 decreases adrenocortical carcinoma (ACC) cell growthin vitroandin vivo
Chimento, A., Sirianni, R., Casaburi, I., Zolea, F., Rizza, P., Avena, P., Malivindi, R., Luca, A. D., Campana, C., Martire, E., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4241 · Cited by 50
Wang, C., Lv, X., Jiang, C., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048299 · Cited by 45
Self-citationBroselid, S., Cheng, B., Sjöström, M., Lövgren, K., Santiago, H. L. P. K.-D., Belting, M., Jirström, K., Malmström, P., Olde, B., Bendahl, P., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2376 · Cited by 44
Hua, G., He, C., Lv, X., Fan, L., Wang, C., Remmenga, S. W., Rodabaugh, K. J., Yang, L., Lele, S. M., Yang, P., et al. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.207 · Cited by 40
Self-citationZhang, Q., Wu, Y., Zhang, Y., Ji, X., & Hao, Q. (2015) · Cell Biochemistry and Function · doi:10.1002/cbf.3097 · Cited by 38
Skrzypczak, M., Schüler, S., Lattrich, C., Ignatov, A., Ortmann, O., & Treeck, O. (2013) · Steroids · doi:10.1016/j.steroids.2013.07.007 · Cited by 35
Kambhampati, S., Rajewski, R. A., Tanol, M., Haque, I., Das, A. K., Banerjee, S., Jha, S. S., Burns, D. M., Borrego-Diaz, E., Veldhuizen, P. J. V., et al. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-0777 · Cited by 28
Kurt, A. H., Çelik, A., & KELLECİ, B. M. (2015) · Oncology Letters · doi:10.3892/ol.2015.3711 · Cited by 27
Ruan, S.-Q., Wang, S.-W., Wang, Z.-H., & Zhang, S.-Z. (2012) · Molecular Medicine Reports · doi:10.3892/mmr.2012.874 · Cited by 24
Self-citationAntihormones in Prevention and Treatment of Breast Cancer
Ponzone, R., Biglia, N., Jacomuzzi, M. E., Mariani, L. L., Dominguez, A., & Sismondi, P. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1386.037 · Cited by 24
Lubig, J., Lattrich, C., Springwald, A., Häring, J., Schüler, S., Ortmann, O., & Treeck, O. (2012) · Cancer Investigation · doi:10.3109/07357907.2012.666690 · Cited by 14
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ASGARD is a single-cell guided pipeline to aid repurposing of drugs
He, B., Xiao, Y., Liang, H., Huang, Q., Du, Y., Li, Y., Garmire, D., Sun, D., & Garmire, L. X. (2023) · Nature Communications · doi:10.1038/s41467-023-36637-3 · Cited by 57
Metadata
- Authors
- Lv, X., He, C., Huang, C., Hua, G., Wang, Z., Remmenga, S. W., Rodabough, K. J., Karpf, A. R., Dong, J., Davis, J. S., & Wang, C.
- Affiliations
- University of Nebraska Medical Center (US)
- Huazhong Agricultural University (CN)
- First Affiliated Hospital of Zhengzhou University (CN)
- Fred and Pamela Buffett Cancer Center (US)
- Omaha VA Medical Center (US)
- Corresponding author
- Wang, Cheng
- ORCID
- Venue
- Molecular Cancer Therapeutics
- Published
- 2017-06-01
- Volume
- 16
- Issue
- 6
- Pages
- 1080-1091
- ISSN
- 1535-7163 (ISSN-L)
- 1538-8514
- PMC
- PMC5457708
- OpenAlex
- W2592111594
- Cited by
- 53
- References
- 50
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 8 · 2023: 9 · 2022: 9 · 2021: 7 · 2020: 4 · 2019: 6 · 2018: 3
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Cancer Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 BX000512)
- National Cancer Institute (R01CA201500, R01CA197976)
- National Institute of General Medical Sciences (P30GM106397, R01GM109066)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R00HD059985)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Physical Sciences › Chemistry › Organic Chemistry › Heterocyclic Compound Synthesis and Bioactivity
- Keywords
- G-1, G protein-coupled estrogen receptor, breast cancer, triple-negative breast cancer, colchicine binding site, tubulin, microtubule assembly, mitotic spindle, mitotic arrest, apoptosis, caspase activation, 2-methoxyestradiol
- MeSH terms
- Animals, Antineoplastic Agents, Binding Sites, Cell Cycle, Cyclopentanes, Disease Models, Animal, Female, Humans, Microtubules, Protein Binding, Quinolines, Receptors, Estrogen, Tubulin, Apoptosis, Xenograft Model Antitumor Assays, Cell Line, Tumor, Cell Proliferation, Tubulin Modulators, Mice, Protein Multimerization
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