TARGETING MITOCHONDRIAL PEPTIDE HUMANIN TO IMPROVE CHEMOSENSITIVITY IN GLIOBLASTOMA CELLS

AGUDELO, JORGE A. PEÑA; PIDRE, MATIAS L.; ASAD, ANTONELA S; GARCIA FALLIT, MATÍAS; KUPER, MELANIE PÉREZ; NICOLA CANDIA, ALEJANDRO J; GLIENKE, LEILANE; SAGRIPANTI, SOFIA; MARCHESINI ABRIL; MORALES, LESLIE C. AMORÓS; VERA, MARIANA B.; GONZALEZ, NAZARENO; VIDELA-RICHARDSON, GUILLERMO A.; SEILICOVICH, ADRIANA; CANDOLFI, MARIANELA

Congreso; Reunión anual de la SAIC; 2022

Humanin (HN) is a mitochondrial peptide with a robust cytoprotective many cell types. HN can interact with proteins of the bcl-2 family or be released and bind with two membrane receptors: a trimetric receptor, and the FPR-2 receptor. HN protects normal tissues from chemotherapy, and the administration of HN analogs has been proposed as a therapeutic approach for degenerative diseases. However, its role on the pathogenesis of cancer is poorly understood. Here we aimed to evaluate whether HN affects chemo-resistance of glioblastoma (GBM) cells. We first assessed the effect of chemotherapy on HN expression in murine (GL26) and human (U251) GBM cell lines, as well as in primary cultures from GBM biopsies. By immunofluorescence we observed that cisplatin upregulates HN in all the cells evaluated. To analyze the effect of HN on chemotherapeutic cytotoxicity, we used a HN analog peptide (HNG). In human GBM cells we observed that HNG abolished the cytotoxic and antiproliferative effect of cisplatin, restoring viability and clonogenic capacity (Two-way ANOVA p