Identification of Breast Cancer Inhibitors Specific for G Protein-Coupled Estrogen Receptor (GPER)-Expressing Cells
Autor: | Marco Radi, Alessandra Nigro, Elena Spina, Gabriele Costantino, Gabriele Carullo, Sabrina Tassini, Francescsa Aiello, Francesca Giordano, Antonio Garofalo, Agostino Bruno, Paolo Vincetti |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Cyclin-Dependent Kinase Inhibitor p21 medicine.drug_class Cell Survival Estrogen receptor Antineoplastic Agents Breast Neoplasms Biology Pharmacology Biochemistry Receptors G-Protein-Coupled 03 medical and health sciences Breast cancer Breast cancer cell line Cell Line Tumor Quinoxalines Drug Discovery medicine Estrogen Receptor beta Humans Cyclin D1 General Pharmacology Toxicology and Pharmaceutics Cell Proliferation Virtual screening Binding Sites Organic Chemistry Estrogen Receptor alpha medicine.disease Protein Structure Tertiary Molecular Docking Simulation 030104 developmental biology HEK293 Cells Estrogen Cancer research MCF-7 Cells Molecular Medicine Female Signal transduction Cancer cell lines Tumor Suppressor Protein p53 GPER |
Zdroj: | ChemMedChem. 12(16) |
ISSN: | 1860-7187 |
Popis: | Together with estrogen receptors ERα and ERβ, the G protein-coupled estrogen receptor (GPER) mediates important pathophysiological signaling pathways induced by estrogens and is currently regarded as a promising target for ER-negative (ER-) and triple-negative (TN) breast cancer. Only a few selective GPER modulators have been reported to date, and their use in cancer cell lines has often led to contradictory results. Herein we report the application of virtual screening and cell-based studies for the identification of new chemical scaffolds with a specific antiproliferative effect against GPER-expressing breast cancer cell lines. Out of the four different scaffolds identified, 8-chloro-4-(4-chlorophenyl)pyrrolo[1,2-a]quinoxaline 14 c was found to be the most promising compound able to induce: 1) antiproliferative activity in GPER-expressing cell lines (MCF7 and SKBR3), similarly to G15; 2) no effect on cells that do not express GPER (HEK293); 3) a decrease in cyclin D1 expression; and 4) a sustained induction of cell-cycle negative regulators p53 and p21. |
Databáze: | OpenAIRE |
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