NSCA-1; A Novel N-substituted Coumalamide Derivative; Increases Adriamycin Sensitivity in HepG2/adriamycin Cells through Modulating Akt/GSK-3 β Signaling and p53-dependant Apoptotic Pathway

In this study, we report the synthesis and biological evaluation of a novel N-substituted coumalamide derivative (NSCA-1). The results indicated that NSCA-1 exerts synergistic cytotoxicity with Adriamycin in HepG2/ADR (HepG2/adriamycin) cells. Furthermore, both of the Akt kinase activity and phosphorylated Akt (Ser473) were found to be inhibited by NSCA-1 and subsequently resulting in decreased phosphorylation of GSK-3β. The intracellular accumulation of Adriamycin was also boosted by NSCA-1 via reducing the expression of p-gp. In addition, we found that combined treatment with NSCA-1 enhance cell apoptosis induced by Adriamycin via p53-dependant apoptotic pathway.
Source: Environmental Toxicology and Pharmacology - Category: Environmental Health Source Type: research