**Acknowledgements**

**5. Conclusion**

148 Liver Cancer

The pathophysiology of HCC is multifactorial and involves mitochondrial dysfunction. Mitochondria usually generate relevant modulators of gene expression controlled by epigenetic mechanisms. These alterations induce chromosomic instability that could give advantages to subclones of cells to their outgrowth (**Figure 1**). Further studies are needed to find

**Figure 1.** (**A)** In the model of liver injury induced by diethylnitrosamine (DEN), the architecture of the liver parenchyma is altered causing an exacerbated proliferation of various transformed clones, where the presence of a large number of tumors randomly distributed in each one is observed in the hepatic lobules. The preneoplastic nodules that form are surrounded by septa of collagen fibers; thus, favoring the evasion of the immune system and an ideal hypoxic microenvironment for the tumor cells. The genomic instability caused by the toxic as well as favoring mutations, for example in p53, and various alterations in different cellular modulators, among them HGF, c-Met, PCNA, gankyrin and p27. It also causes an increase of proteins, deacetylating PGC1-α, and, thus, modifies various nuclear genes exported to the mitochondria, causing accumulation of abnormal and dysfunctional mitochondria. (**B)** In the model of hepatocarcinoma induced by DEN, the administration of the adenosine derivative, IFC-305, has been shown to have various regulatory effects. The excessive accumulation of collagen fibers in preneoplastic nodules as well as the number and size of tumors are reduced. Also, cell morphology and DNA recover significantly. A decrease in the deacetylase Sirt-1, whose target is PCG1-α, has been observed, which allows the latter to remain acetylated and can be internalized to mitochondria, where it will promote its adequate morphology, dynamics and function. It has also been found that the compound IFC-305 acts on the levels of some important modulators in cancer (p53, HGF, C-Met…), maintaining or returning them to their concentrations under

normal conditions. Overall, the aforementioned effects make this compound a possible therapeutic alternative.

This work was supported by Consejo Nacional de Ciencia y Tecnología (240315) and DGAPA-UNAM, grant numbers IN208915 VCS.
