Science and Technology Production
Congress
Authorship
Hidalgo, Florencia
;
Tonucci, Facundo
;
Almada, Evangelina
;
Pariani, Alejandro
;
Larocca, M. Cecilia
;
FAVRE, CRISTIAN
Date
2018
Publishing House and Editing Place
Medicina (Buenos Aires)
Summary
Information provided by the agent in
SIGEVA
Hepatocellular carcinoma (HCC) is the second lethal cancer, which is in part due to both its high metastatic capacity and resistance to current therapies. In these sense we focus in the activation of the kinase AMPK as an antitumor strategy because it has been found to be negatively regulated in HCC, and that its activity is inversely associated to more aggressive forms of the disease. Previously, we showed that α-Lipoic acid (aLA), proposed as an anti-cancer agent associated with AMPK ac...
Hepatocellular carcinoma (HCC) is the second lethal cancer, which is in part due to both its high metastatic capacity and resistance to current therapies. In these sense we focus in the activation of the kinase AMPK as an antitumor strategy because it has been found to be negatively regulated in HCC, and that its activity is inversely associated to more aggressive forms of the disease. Previously, we showed that α-Lipoic acid (aLA), proposed as an anti-cancer agent associated with AMPK activation, increased cell death and decreased cell migration in HCC cell lines, among other effects. In this stage of the study we were interested in analyzing the impact of aLA treatment in cell invasiveness and deepening into the signaling pathway involved, both upstream and downstream AMPK. To achieve this goal we attempted to determinate if LKB1 participated in the signaling pathway, and also look at p53 due to it is an AMPK target whose stabilization by aLA was previously described in literature. Our results showed that p-AMPK(Thr172) levels were increased in aLA (0.5-1 mM) treated cells, at the same time that total and cytosolic levels of LKB1 were increased. We measured the level of phosphorylation of p53(Ser17) and found it was increased by aLA in HepG2/C3A cells, and this was in accordance with the fact that the same treatment signifcantly decreased migration in HepG2/C3A (p53 WT) but not in Hep3B (p53 null) hepatocarcinoma cells. On the other hand, the treatment with aLA (0.5 mM) signifcantly (p=0.00014) decreased by half the invasive capacity of HCC cells, in Matrigel-coated invasion chamber assays. These fndings allow us to conclude that aLA not only increases apoptosis but also decreases invasiveness of HCC cells and to propose that an LKB1/ AMPK/p53 pathway is a possible axis through which aLA could exert its anti tumor effects.
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Key Words
SEÑALIZACIÓNAMPKCARCINOMA HEPATOCELULAR