Interaction of Mitochondrial and Epigenetic Regulation in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a pathology preceded mainly by cirrhosis of diverse etiology and is associated with uncontrolled dedifferentiation and cell proliferation processes. Many cellular functions are dependent on mitochondrial function, among which we can mention the enzymatic activity of PARP-1 and sirtuin 1, epigenetic regulation of gene expression, apoptosis, and so on. Mitochondrial dysfunction is related to liver diseases including cirrhosis and HCC; the energetic demand is not properly supplied and mitochondrial morphologic changes have been observed, resulting in an altered metabolism. There is a strong relationship between epigenetics and mitochondrion since the first one is dependent on the correct function of the last one. There is an interest to improve or to maintain mitochondrial integrity in order to prevent or reverse HCC; such is the case of IFC-305 that has a beneficial effect on mitochondrial function in a sequential model of cirrhosis-HCC. In this model, IFC-305 downregulates the expression of PCNA, thymidylate synthase, HGF and its receptor c-Met and upregulates the cell cycle inhibitor p27, thereby decreasing cell proliferation. Both effects, improvement of mitochondria function and reduction of tumor proliferation, suggest its use as HCC chemoprevention or as an adjuvant in chemotherapy