Involvement of p53 in the cytotoxic activity of the NAMPT inhibitor FK866 in myeloid leukemic cells

摘要: FK866 is a specific inhibitor of NAMPT and induces apoptosis leukemic cells by depletion intracellular NAD+. Since up-regulation associated with several cases cancers, including leukemias, we asked whether in inhibition involves p53 pathway. We observed that induced reduced cell proliferation NB-4, OCI-AML3 MOLM-13 lines. In contrast, the leukemia lines, K-562 Kasumi, containing nonfunctional were relatively unaffected treatment. Importantly, direct sirtuins significantly viability Activation involved increased acetylation at lysine 382 subsequent increase expression p21 BAX. Further, knockdown attenuated effects on cycle arrest, which was partly decreased Our results suggest role pathway anti-leukemic effect FK866.