Reactive oxygen species as signaling molecules in liver carcinogenesis

CARRILLO, MARIA CRISTINA; ALVAREZ, MARIA DE LUJAN; PARODY, JUAN PABLO; QUIROGA, ARIEL DARIO; CEBALLOS, MARIA PAULA

Lipid Peroxidation

InTech

Año: 2012; p. 315 - 344

Reactive Oxygen Species (ROS) are essential participants in cell signaling and regulation of many gene- and enzyme-catalyzed processes. Therefore, ROS signaling can initiate both inhibition and activation of tumor formation. In this chapter, we summarize a series of experiments that have allowed us to establish the role of oxidative stress in the early development of liver cancer process (known as liver preneoplasia), and the effects of cytokines on the modulation of this process. We demonstrated that preneoplastic hepatocytes are more resistant to oxidative stress than normal ones. Treatment of preneoplastic livers with Interferon α-2b (IFN α-2b) induced an increase in ROS levels that mediated the process of programmed cell death, leading to the elimination of malignant cells. The induction of NADPH oxidase activity via p38 MAPK activation was the main pathway of ROS production. The study of the mechanism of IFN α-2b-induced apoptosis led to demonstrate a link between IFN α-2b and transforming growth factor β1 (TGFβ1), and also an association between IFN α-2b, Wnt signaling and the oxidative stress/FOXO pathways. In conclusion, reactive oxygen species emerge as key mediators in the context of using cytokines as therapeutic agents in the treatment of human liver diseases, so the use of antioxidants could have the potential to decrease effectiveness of the therapy.