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The novel Mas agonist, CGEN 856S, promotes Akt/eNOS activation and anti‐proliferation with FOXO1 involvement (1097.3)
Author(s) -
Peluso Antonio,
PassosSilva Danielle,
Etelvino Gisele,
Rotman Galit,
Santos Robson
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1097.3
Subject(s) - wortmannin , foxo1 , du145 , protein kinase b , chemistry , a549 cell , pi3k/akt/mtor pathway , enos , chinese hamster ovary cell , cell growth , transfection , microbiology and biotechnology , pharmacology , cancer research , medicine , cell , apoptosis , biology , receptor , lncap , biochemistry , cancer cell , nitric oxide synthase , enzyme , cancer , gene
Biotechnology advances allowed the discovery of a potential Mas agonist, CGEN 856S, which produces several effects resembling those produced by Angiotensin‐(1‐7). This study evaluated the effect of CGEN 856S on FOXO1 and Akt/eNOS activation, using different cell types. HAEC (Human Aortic Endothelial Cell), A549 and DU145 (human tumoral linages from lungs and prostate, respectively) cell were treated with CGEN 856S with or without previous treatment with A779. The cells were used for immunolocalization of FOXO1, analyzed by confocal microscopy and the nuclear fluorescence intensity was quantified. Mas‐transfected CHO (chinese hamster ovary) cells were stimulated with CGEN 856S. Untransfected CHO cells were used as control and the proteins were used for phospho‐Akt, phospho‐eNOS, phosphor‐FOXO1, Mas and GAPDH detection by western blot. A549 and DU145 cells were also used for cytotoxicity test, being treated with CGEN856S with a combination of PI3 kinase inhibitors, Wortmannin or LY294002, in different concentrations. The results showed a significant nuclear translocation of FOXO1 in HAEC, A549 and DU145 cell types treated with CGEN 856S. The Mas antagonist A779 attenuated to a great extent this effect. The phosphorylation of Akt, eNOS as well as the dephosphorylation of FOXO1 in CHO‐Mas cells treated with CGEN856S was significant. In both DU145 and A549 cells, the combination of the PI3 kinase inhibitors with CGEN 856S was able to potentiate it anti‐proliferative effect. These data suggest that CGEN 856S induces its effects similarly to Ang‐(1‐7), via Mas receptor. Grant Funding Source : Supported by CNPq/MCTI/FAPEMIG #573924/2008‐2