Role of AMPK-p53 pathway in the antimigratory effects of alpha lipoic acid in hepatocellular carcinoma cells.

HIDALGO F; BAFFO E; FERRETTI AC; PARIANI A; LAROCCA MC; FAVRE C

Rosario

Congreso; Reunión Anual de la Sociedad Argentina de Fisiología (SAFIS); 2019

SAFIS

Alpha lipoic acid (ALA) is a natural compound, which actsas a cofactor of mitochondrial enzymes and selectivelyinduces mitochondrial dysfunction and cytotoxicity in tumor cells. In addition, ALA antitumor role is associatedto its capacity of AMPK activation. We are focused onstudying less explored effects of ALA on cellmigration/invasion in hepatocellular carcinoma (HCC). Inprevious work we demonstrated that ALA increases celldeath and decreases cell migration and invasion in HCCcells in which an increase in p-AMPK levels is alsoobserved. Some of these effects were enhanced byglucose starvation (GS). It is proposed that energy stressactivates p53 via AMPK in diverse cell types and that AMPKcan induce p53 transcription and/or phosphorylate it andhence stabilize it postranscriptionally. In this part of thestudy, our aim was to analyze to what extent theantimigratory effect of ALA could depend on this kinaseand if p53, which is related to some effects of ALA,participates. For these purposes, we used, on the onehand, AMPKa-silenced HCC cells (AMPK-KD) and on theother hand, p53 null cells, Hep3B. In HCC cell line with wildtype p53 (HepG2/C3A) the levels of p53 expression weremeasured (mRNA by qPCR) after cell culture in DMEMwithout (C), or with 1mM ALA (ALA) for 24 h, and both alsoin conditions of glucose starvation (GS). We found thatmRNA levels were increased (ΔΔCt in arbitrary units C: 1;ALA: 5.85; GS: 6.3; ALA GS: 7.65, p