Together with ERα/β, GPER (G protein-coupled estrogenreceptor) mediates important pathophysiological signaling pathwaysinduced by estrogens and is currently regarded as a promising targetfor ER-negative and triple-negative breast cancer. Only a fewselective GPER modulators have been reported to date and theiruse in cancer cell lines has often led to contradictory results. Herewe report the application of virtual screening and cell-based studiesfor the identification of new chemical scaffolds with a specific antiproliferativeeffect against GPER-expressing breast cancer cell lines.Out of the four different scaffolds identified, the pyrrolo[1,2-a]quinoxaline 14c was found as the most promising compound ableto induce i) antiproliferative activity in GPER expressing cell lines(MCF7 and SKBR3) similar to G15, ii) no effect on cells that do notexpress the GPER receptor (HEK293), iii) reduction in Cyclin D1expression, and iv) sustained induction of the cell cycle negativeregulators p53 and p21.
Together with ERα/β, GPER (G protein-coupled estrogenreceptor) mediates important pathophysiological signaling pathwaysinduced by estrogens and is currently regarded as a promising targetfor ER-negative and triple-negative breast cancer. Only a fewselective GPER modulators have been reported to date and theiruse in cancer cell lines has often led to contradictory results. Herewe report the application of virtual screening and cell-based studiesfor the identification of new chemical scaffolds with a specific antiproliferativeeffect against GPER-expressing breast cancer cell lines.Out of the four different scaffolds identified, the pyrrolo[1,2-a]quinoxaline 14c was found as the most promising compound ableto induce i) antiproliferative activity in GPER expressing cell lines(MCF7 and SKBR3) similar to G15, ii) no effect on cells that do notexpress the GPER receptor (HEK293), iii) reduction in Cyclin D1expression, and iv) sustained induction of the cell cycle negativeregulators p53 and p21.
Identification of Breast Cancer Inhibitors Specific for G Protein -Coupled Estrogen Receptor (GPER)-Expressing Cells
AIELLO, Francesca;CARULLO, GABRIELE;GIORDANO, Francesca;Elena Spina;Alessandra Nigro;Antonio Garofalo;
2017-01-01
Abstract
Together with ERα/β, GPER (G protein-coupled estrogenreceptor) mediates important pathophysiological signaling pathwaysinduced by estrogens and is currently regarded as a promising targetfor ER-negative and triple-negative breast cancer. Only a fewselective GPER modulators have been reported to date and theiruse in cancer cell lines has often led to contradictory results. Herewe report the application of virtual screening and cell-based studiesfor the identification of new chemical scaffolds with a specific antiproliferativeeffect against GPER-expressing breast cancer cell lines.Out of the four different scaffolds identified, the pyrrolo[1,2-a]quinoxaline 14c was found as the most promising compound ableto induce i) antiproliferative activity in GPER expressing cell lines(MCF7 and SKBR3) similar to G15, ii) no effect on cells that do notexpress the GPER receptor (HEK293), iii) reduction in Cyclin D1expression, and iv) sustained induction of the cell cycle negativeregulators p53 and p21.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
