Inhibition of NAMPT sensitizes MOLT4 leukemia cells for etoposide treatment through the SIRT2-p53 pathway.

摘要: NAMPT (Nicotinamide phosphoribosyltransferase) catalyses the rate-limiting step in NAD biosynthesis from nicotinamide and thereby regulates activity of NAD-dependent enzymes. Cancer cells are highly dependent on for energy DNA repair processes assumed to be more susceptible an inhibition synthesis than non-transformed cells. We aimed investigate whether or not with its specific inhibitor FK866 can sensitize leukemia chemotherapeutic agents. protein abundance, enzymatic concentrations were significantly higher Jurkat Molt-4 cell lines compared normal peripheral blood mononuclear Combination etoposide caused increased death alone. Etoposide decreased abundance deacetylases SIRTUIN1. After combining treatment SIRTUIN2 was further accumulation acetylation downstream target p53 enhanced MOLT4 Concomitantly, p21 cleaved BAX increased. Targeting could a novel therapeutic strategy enhance efficacy agents such as against leukemia.