IFN-α-2b induces apoptosis by decreasing cellular cholesterol levels in rat preneoplastic hepatocytes.

Autor: Quiroga AD; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, Argentina; CAECIHS, Universidad Abierta Interamericana, Rosario, Argentina. Electronic address: quiroga@ifise-conicet.gov.ar., Vera MC; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina. Electronic address: vera@ifise-conicet.gov.ar., Ferretti AC; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, Argentina. Electronic address: ferretti@ifise-conicet.gov.ar., Lucci A; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, Argentina. Electronic address: lucci@ifise-conicet.gov.ar., Comanzo CG; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina. Electronic address: comanzo@ifise-conicet.gov.ar., Lambertucci F; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina. Electronic address: lambertucci@ifise-conicet.gov.ar., Ceballos MP; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina. Electronic address: ceballos@ifise-conicet.gov.ar., Carrillo MC; Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Rosario, Argentina; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, Argentina. Electronic address: carrillo@ifise-conicet.gov.ar.
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2020 Sep; Vol. 133, pp. 155172. Date of Electronic Publication: 2020 Jun 24.
DOI: 10.1016/j.cyto.2020.155172
Abstrakt: IFN-α administration to patients has been long discouraged and pushed back by new and apparently better drugs; however the adverse secondary effect, the high costs and the lack of specific action, make these new drugs hard to be used and put IFN-α again in the eye of the researchers. IFN-α-2b was demonstrated to induce apoptosis and modulation of lipid metabolism and the mechanisms are still unknown. Here, we sought to find the link between these features using a model of early stage cancer development. Using in vitro and in vivo approaches, we evaluated apoptosis and lipid metabolism. IFN-α-2b induced changes in hepatic cholesterol mass due to decreased synthesis and increased secretion. Interestingly, the drop in cellular cholesterol levels was necessary for IFN-α-2b to induce apoptosis. Results presented in this paper show the complexity of the action of IFN-α-2b on the early stages of liver cancer development. We show for the first time an interrelationship between cholesterol, apoptosis and IFN-α-2b. This makes clear the need for a reevaluation of IFN-α-2b action in order to develop softer, safer and more bearable derivatives. In this regard, knowing the molecular mechanisms by which IFN-α exerts its cellular actions is of crucial importance, and it is the main condition for therapy success for classical and new malignancies.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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