The interlacing anticancer effect of pharmacologic ascorbate, chloroquine, and resveratrol

Our present study first described that the combined Ph-Asc, Res, and CQ co-treatment exerted a synergistic cytotoxic effect on KRAS mutant PDAC cells. Both Ph-Asc and Res caused DSBs in the DNA, accompanied by cell cycle arrest and cell death. Ph-Asc-induced cytotoxicity shows strong ROS dependence, while Res-induced cytotoxicity seems to be independent of ROS generation; Res treatment induced significant elevation of caspase-3/7 activity while Ph-Asc-induced cell death proved to be caspase-independent. The fact that both Ph-Asc and Res are natural compounds without significant harmful effects on normal cells, and the third compound, CQ, is a known antimalarial drug that can easily be repurposed, gives the real importance of our results. AbstractCurrently, a diagnosis with KRAS mutant pancreatic ductal adenocarcinoma (PDAC) means a death warrant, so finding efficient therapeutic options is a pressing issue. Here, we presented that pharmacologic ascorbate, chloroquine and resveratrol co-treatment exerted a synergistic cytotoxic effect on PDAC cell lines. The observed synergistic cytotoxicity was a general feature in all investigated cancer cell lines independent of the KRAS mutational status and seems to be independent of the autophagy inhibitory effect of chloroquine. Furthermore, it seems that apoptosis and necroptosis are also not likely to play any role in the cytotoxicity of chloroquine. Both pharmacologic ascorbate and resveratrol caused double-strand DNA breaks accompan...
Source: BioFactors - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research