A critical role of autophagy in antileukemia/lymphoma effects of APO866, an inhibitor of NAD biosynthesis

摘要: APO866, an inhibitor of NAD biosynthesis, exhibits potent antitumor properties in various malignancies. Recently, it has been shown that APO866 induces apoptosis and autophagy human hematological cancer cells, but the role APO866-induced cell death remains unclear. Here, we report studies on molecular mechanisms underlying with emphasis autophagy. Treatment leukemia lymphoma cells induced both autophagy, as evidenced by increase autophagosome formation SQSTM1/p62 degradation, also increased caspase activation revealed CASP3/caspase 3 cleavage. As mechanism, APO866-mediated was found to deplete CAT/catalase, a reactive oxygen species (ROS) scavenger, thus promoting ROS production death. Inhibition ATG5 or ATG7 silencing prevented CAT production, activation, Finally, supplementation exogenous abolished cytotoxic activity. Altogether, our results indicated is essential for activity from malignancies indicate autophagy-dependent novel mechanism killing. Autophagy-modulating approaches could be new way enhance related agents.