Interferon alfa-2b triggers transforming growth factor-β1-induced apoptosis on preneoplastic liver

Considerable expectations to prevent hepatocellular carcinoma (HCC) appearance are connected with the use of Interferon α (IFN α) in antiviral treatment of hepatitis B or C. Several studies have reported that the incidence of HCC may be reduced after IFN therapy in patients with chronic B or C hepatitis although its real preventive effect is still debatable. The purpose of the studies from our laboratory was to evaluate the action of IFN a2b on preneoplastic foci in a two-phase model of preneoplasia development in rat. We demonstrated that IFN-α2b administration significantly decreased both number and volume percentage of altered hepatic foci (AHF). This reduction could be explained by an induced programmed cell death in the foci. This apoptotic effect of IFN-α2b on preneoplastic liver foci was mediated by the production of endogenous TGF/31 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-α2b. In conclusion, IFN-α2b could enhance the proapoptotic effects of TGF/β1 in early stages of hepatocarcinogenesis, which could be highly beneficial in cancer therapy.