Enrique Chávez1, María Guadalupe Lozano-Rosas1, Mariana Domínguez-López1, Gabriela Velasco-Loyden1, Jesús Rafael Rodríguez-Aguilera1, Concepción José-Nuñez1, Marietta Tuena de Gómez-Puyou1, Victoria Chagoya de Sánchez2. 1. Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (E.C., M.G.L.-R., M.D.-L., G.V.-L., J.R.R.-A., V.C.S.); and Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (C.J.-N., M.T.G.-P.). 2. Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (E.C., M.G.L.-R., M.D.-L., G.V.-L., J.R.R.-A., V.C.S.); and Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico (C.J.-N., M.T.G.-P.) vchagoya@ifc.unam.mx.
Abstract
Background: Mitochondrion is an important metabolic and energetic organelle that regulates several cellular processes. Mitochondrial dysfunction has been related to liver diseases including hepatocellular carcinoma. As a result, the energetic demand is not properly supplied and mitochondrial morphologic changes have been observed, resulting in an altered metabolism. We previously demonstrated the chemopreventive effect of the hepatoprotector IFC-305. Aim: In this work we aimed to evaluate the functional, metabolic, and dynamic mitochondrial alterations in the sequential model of cirrhosis-hepatocellular carcinoma induced by diethylnitrosamine in rats and the possible beneficial effect of IFC-305. Methods: Experimental groups of rats were formed to induce cirrhosis-hepatocellular carcinoma and to assess the IFC-305 effect during cancer development and progression through the evaluation of functional, metabolic, and dynamic mitochondrial parameters. Results: In this experimental model, dysfunctional mitochondria were observed and suspension of the diethylnitrosamine treatment was not enough to restore them. Administration of IFC-305 maintained and restored the mitochondrial function and regulated parameters implicated in metabolism as well as the mitochondrial dynamics modified by diethylnitrosamine intoxication. Conclusion: This study supports IFC-305 as a potential hepatocellular carcinoma treatment or as an adjuvant in chemotherapy.
Background: Mitochondrion is an important metabolic and energetic organelle that regulates several cellular processes. Mitochondrial dysfunction has been related to liver diseases including hepatocellular carcinoma. As a result, the energetic demand is not properly supplied and mitochondrial morphologic changes have been observed, resulting in an altered metabolism. We previously demonstrated the chemopreventive effect of the hepatoprotector IFC-305. Aim: In this work we aimed to evaluate the functional, metabolic, and dynamic mitochondrial alterations in the sequential model of cirrhosis-hepatocellular carcinoma induced by diethylnitrosamine in rats and the possible beneficial effect of IFC-305. Methods: Experimental groups of rats were formed to induce cirrhosis-hepatocellular carcinoma and to assess the IFC-305 effect during cancer development and progression through the evaluation of functional, metabolic, and dynamic mitochondrial parameters. Results: In this experimental model, dysfunctional mitochondria were observed and suspension of the diethylnitrosamine treatment was not enough to restore them. Administration of IFC-305 maintained and restored the mitochondrial function and regulated parameters implicated in metabolism as well as the mitochondrial dynamics modified by diethylnitrosamine intoxication. Conclusion: This study supports IFC-305 as a potential hepatocellular carcinoma treatment or as an adjuvant in chemotherapy.
Authors: Jun Chen; Evan LaGue; Junjie Li; Chendong Yang; Edward P Hackett; Manuel Mendoza; Jeffry R Alger; Ralph J DeBerardinis; Ian R Corbin; Kelvin L Billingsley; Jae Mo Park Journal: Anal Sens Date: 2021-09-14
Authors: Kelsey L McLaughlin; Margaret A M Nelson; Hannah S Coalson; James T Hagen; McLane M Montgomery; Ashley R Wooten; Tonya N Zeczycki; Nasreen A Vohra; Kelsey H Fisher-Wellman Journal: Front Oncol Date: 2022-06-08 Impact factor: 5.738