Reactive species as signaling molecules in liver carcinogenesis

CARRILLO M C; ALVAREZ, MARÍA DE LUJÁN; QUIROGA A D; PARODY J P; CEBALLOS M P

Lipid peroxidation

Catala, A

Año: 2012; p. 315 - 344

Reactive Oxygen Species (ROS) were viewed as the ‘‘bad’’ molecules of cells for a long time, but in the recent years, several lines of evidence indicate the contrary: ROS are essential participants in cell signaling and regulation depending on their concentration.At present it is well established that ROS signaling is an important factor of many gene- and enzyme-catalyzed processes. ROS signaling is responsible for activation or inhibition of numerous processes catalyzed by protein kinases, phosphatases, and many other enzymes although these reactions proceed by heterolytic (non-free radical) mechanisms.Therefore, ROS signaling can initiate both inhibition and activation of tumor formation. This fact might be of utmost importance for the development of anticancer treatment by thedrugs possessing both prooxidant and antioxidant properties.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 and the effects of cytokines on the modulation of this process.Through a series of in vivo and in vitro experiments we are able to describe:The oxidative stress status of a preneoplastic liverThe modulating effect of Interferon alfa-2b (IFN alfa-2b) on this oxidative status that triggersthe apoptotic mechanism in hepatic cellsThe role of TGFbeta1 in the whole processThe participation of FOXO transcription family proteins in the programmed cell deathactivated by IFN alfa-2b and TGFbeta1.