Contribution of MAPKs pathways, PI3K/AKT and ER stress to murine melanoma cell death induced by a triazolyl peptidyl penicillin

BELLIZI, Y.; ANSELMI RELATS, J.M.; CORNIER, P.G.; DELPICCOLO, C.M.L.; MATA, E.G.; BLANK, V.C.; ROGUIN, L.P.

Congreso; Reunión Anual de Sociedades de Biociencias; 2020

The triazolyl peptidyl penicillins (TAPs) are novel hybrids compounds having in their structure a penicillanic core linked to a peptide portion via a triazole group. In a previous study, we showed that the derivative containing the dipeptide Leu-Phe (TAP7f) triggers an endoplasmic reticulum (ER) stress response, induces apoptosis and activates p38, JNK and PI3K-I/AKT pathways in murine B16-F0 melanoma cells. In order to investigate the role of these signaling cascades in the mechanism of action of TAP7f, B16-F0 cells were transfected with specific mutant dominant negative constructs or control vectors and treated with TAP7f. Results showed an increase in cell proliferation from 26±3% (control vector) to 42±4, 36±3, 38±4% after transfecting cells with p38, JNK or PI3K-I dominant negative mutants, respectively (*p