Role of autophagy in the chemopreventive effect of the IFC-305 compound in the sequential model of cirrhosis-hepatocellular carcinoma in the rat and in vitro.

Abstract

Hepatocellular carcinoma (HCC) can be originated from various etiologies and is preceded mostly by cirrhosis. Unfortunately, there is no effective treatment due to its late prognosis. Alterations in autophagy have been reported during the development and progression of HCC. Autophagy allows for the maintenance of a positive energy balance and the proper functioning of organelles through the selective degradation of cellular components. It has been demonstrated that autophagy suppresses spontaneous tumorigenesis in the liver. Therefore, autophagy has become a therapeutic target for effective HCC therapies. We have previously demonstrated that the adenosine-derived compound, IFC-305, has a chemopreventive effect on HCC, in addition to maintaining mitochondrial function in a sequential model of cirrhosis-HCC. Thus, the aim of this work was to determine if IFC-305 has an effect on autophagy in the sequential model of cirrhosis-HCC induced by diethylnitrosamine or in vitro in the HCC cell line HepG2 and mouse embryonic fibroblasts. The results of this work showed that IFC-305 modifies the levels of the BECN1, p62/SQSTM1 and LC3-II proteins that play an important role in the autophagic process. In vivo, IFC-305 regulates the levels of the PINK1 and PARKIN proteins that specifically mark mitochondria for repair or degradation. In the HepG2 cell line, its effect was accompanied by a decrease in cell viability. Interestingly, in nontumoral cells the time to autophagy induction was different compared to the HepG2 cells. This study suggests that autophagy induction may be part of the mechanism by which IFC-305 maintains mitochondrial function, thereby facilitating the prevention and reversal of HCC.

• Authors: Enrique Chávez, Gabriela Velasco-Loyden, María Guadalupe Lozano-Rosas, Beatriz Aguilar-Maldonado, Gabriel Muciño-Hernández, Susana Castro-Obregón, Victoria Chagoya de Sánchez
• Journal: American journal of cancer research (Am J Cancer Res) Vol. 10 Issue 6 Pg. 1844-1856 ( 2020) ISSN: 2156-6976 [Print] United States
• PMID: 32642295 (Publication Type: Journal Article)
• Copyright: AJCR Copyright © 2020.