title: (6-bromo-1,4-dimethyl-9H-carbazol-3-yl-methylene)-hydrazine (carbhydraz) acts as a GPER agonist in breast cancer cells.
abstract: Estrogens control a wide number of aspects of human physiology and play a key role in multiple diseases, including cancer. Estrogens act by binding to and activating the cognate receptor (ER), however numerous studies have revealed that the G protein-coupled receptor named GPR30/GPER mediates also estrogen signals. As ER and GPER share the ability to bind to same compounds, the use of GPER-selective ligands has allowed a better understanding of the biological responses mediated by GPER. In the present study, we designed and synthesized two novel carbazole derivatives and then investigated their ability to interact with and activate the GPER-mediated transduction pathway in breast cancer cells. Both compounds did not activate the classical ER in MCF7 cells, whereas one of the two compounds synthesized triggered through GPER the rapid ERK activation in ER-negative SkBr3 cells, demonstrating a good affinity for GPER in docking studies. The characterization of this novel selective GPER agonist could represent a potential useful tool to provide further insights into the physiopathological role exerted by GPER.
authors: Maria Stefania
authors: MS
authors: Sinicropi
authors: Rosamaria
authors: R
authors: Lappano
authors: Anna
authors: A
authors: Caruso
authors: Maria Francesca
authors: MF
authors: Santolla
authors: Assunta
authors: A
authors: Pisano
authors: Camillo
authors: C
authors: Rosano
authors: Anna
authors: A
authors: Capasso
authors: Antonella
authors: A
authors: Panno
authors: Jean Charles
authors: JC
authors: Lancelot
authors: Sylvain
authors: S
authors: Rault
authors: Carmela
authors: C
authors: Saturnino
authors: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy. marcellomaggiolini@yahoo.it.
authors: Marcello
authors: M
authors: Maggiolini
mesh_terms: D001665:Binding Sites; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology*; D061986:MCF-7 Cells / Q000187:drug effects / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D062105:Molecular Docking Simulation; D010766:Phosphorylation / Q000187:drug effects; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism
chemical_list: C000607171:(6-bromo-1,4-dimethyl-9H-carbazol-3-ylmethylene)hydrazine; D002227:Carbazoles; C109584:GPER1 protein, human; D006834:Hydrazines; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3