Interferon alfa-2b triggers transforming growth factor-beta-induced apoptosis on preneoplasticliver.
Considerable expectations to prevent hepatocellular carcinoma (HCC) appearance are connecte with the use of Inferon alpha (IFN alpha) in antiviral treatment of the hepatitis B or C. Several studies have reported that the incidence of HCC may b reduced after IFN therapy in patients with chronic B or C hepatitis although its real preventive efffect is still debatable. The purpose of the studies from our laboratory was to evaluate the action of IFN alpha2b on preneoplastic foci in a two-phase model of preneoplasia development in rat. We demonstrated that IFN-alpha2b administration significantly decreased both number and volume percentage of altered hepatitis foci (AHF). This reduction could be explained by an induced programmed cell death in the foci. This apoptotic effect of IFN-alpha2b on preneoplastic liver foci was mediated by the production of endogenous TGFbeta1 from hepatocytes acting by a paracrine/autocrine way. Further studies confirmed that these results were a consequence of the perturbation of the redox status induced by the IFN-2b. In conclusion, IFN-alpha2b couldenhance the proapoptotic effects of TGFbeta1, in early stages of hepatocarcinogenesis, which could be highly beneficial in cancer therapy.
Caríllo
Maria Cristina
MC
Instituto de Fisiología Experiemental, Consejo Nacional de Investigaciones Científicas, Universidad Nacional de Rosario, Argentina. mcarill@fbioyf.unr.edu.ar
Alvarez
Maria de Luján
Mde L
Quiroga
Ariel Darío
AD
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000517:prevention & control*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000517:prevention & control; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000517:prevention & control*; D010084:Oxidation-Reduction; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1