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Avaliação dos efeitos antitumorais e antiproliferativos do peptídeo INKKI em células de adenocarcinoma de mama MCF-7

Mariana Daou Verenhitach

Published 2016 in Unknown venue

ABSTRACT

Verenhitach MD. Evaluation of antitumor and antiproliferative effects of the INKKI peptide in breast adenocarcinoma MCF-7 cell line [Dissertation]. São Paulo: "Faculdade de Medicina, Universidade de São Paulo"; 2015. The INKKI is derived from the bovine hidrolisis of β-casein, a cationic and amphipathic peptide, analogous to mastoparan peptide isolated from the venom of the wasp Vespula lewisi. In in vitro studies, INKKI showed selective cytotoxicity in melanoma tumor cell B16F10 in relation to normal cells. In the in vivo tests, INKKI peptide has been shown to be a potent stimulator of the phagocytic activity of treated macrophages and, when applied directly into tumors, reduced tumor mass, decreasing the time progression and metastasis formation, increasing the probability of survival. This work investigated the in vitro effects of tumor peptide INKKI in cell line of human breast adenocarcinoma MCF-7. The tumor cells used were lineages of human breast tumor cells MCF7, MDA-231 and T47D and murine tumor cells (Ehrlich). The normal cells used were fibroblasts and endothelial cells. The study evaluated the cytotoxic activity, cell viability, change of mitochondrial electrical potential, effects on the progression and arrest of the cell cycle and investigation of induced death by apoptosis. The results revealed that peptide presents selective dose-dependent cytotoxicity in tumor cells by modulating negatively the mitochondrial electric potential. The index of cell proliferation of cells treated declined, with the induction of cell cycle arrest at phase G0/G1. The peptide-induced cell death by apoptosis was demonstrated to occur via mitochondrial pathway and in a caspase-independent manner. The INKKI peptide is a potent modulator of antiproliferative and antitumor activities of the breast adenocarcinoma cell line. Descriptors: INKKI; peptide; hidrolysis; caseins; breast neoplasms; apoptosis; caspases.

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