MECHANISM OF ACTION OF A TRIAZOLYL PEPTIDYL PENICILLIN IN MELANOMA CELLS AND SYNERGISTIC ANTITUMOR EFFECT OF ITS COMBINATION WITH THAPSIGARGIN

JUAN M. ANSELMI; YANINA BELLIZI; PATRICIA G. CORNIER; CARINA M. L. DELPICCOLO; ERNESTO G. MATA; VIVIANA C. BLANK; LEONOR P. ROGUIN

Congreso; Reunión Conjunta de Sociedades Biomédicas.; 2021

In a previous study, we demonstrated that TAP7f, a synthetic triazolylpeptidyl penicillin, behaves as an effective antitumor agent and induces an apoptotic response in murine melanoma cells. In this work, we comparatively examined its mechanism of action in murine B16-F0 and human A375 melanoma cells. We first studied the contribution of an endoplasmic reticulum (ER) stress response to the apoptotic effect induced by the derivative. To this end, the expression levels of different ER stress-related proteins were evaluated by Western blot assays in both melanoma cell lines. A significant increase in the amount of ATF4 (≈1.5-2 fold), GADD153/CHOP (≈1.5-2.5 fold), Calnexin (≈2 fold) and GRP78/BIP (≈2-3.5 fold) was observed after incubating B16-F0 cells for 3 h or 6 h with a 20 µM concentration of TAP7f (p