Cytotoxic effects exerted by pentachlorophenol by targeting nodal pro-survival signalling pathways in human pancreatic cancer cells

We report here evidence that exposure of this type of cells to PCP induces caspase-mediated apoptosis, inhibition of the lysosome cysteine protease cathepsin B and mitochondrial membrane depolarization. Beside cellular inhibition of CK2, the analysis of signaling pathways de-regulated in pancreatic cancer cells revealed that PCP causes decreased phosphorylation levels of NF-κB/p65, suppresses its nuclear translocation and leads to activation of JNK-mediated stress response. Surprisingly, exposure to PCP results in increased phosphorylation levels of AKT at the canonical S473 and T308 activation sites supporting previous data showing that AKT phosphorylation is not predictive of tumor cell response to treatment. Taken together, our study provides novel insights into the effects induced by the exposure of pancreatic cancer cells to chlorinated aromatic compounds posing the basis for more advanced studies in vivo.
Source: Toxicology Reports - Category: Toxicology Source Type: research