ABT-737

ABT-737 is a potent and selective inhibitor of B-cell lymphoma-2 (BCL-2) family proteins. The ABT-737 single-agent LC90 values ranged from 100 nM for COG-LL-319 and RS4; 11 cells to low micromolar concentrations for the other five ALL cell lines. ABT-737 efficiently induces apoptosis and suppresses growth of hepatoma cells in combination with sorafenib. Moreover, we observed that the enhancement of ABT-737-mediated apoptosis by NCTD was associated with activation of mitochondrial apoptosis signaling pathway, which involved cytosolic release of cytochrome c, cleavage of caspase-9 and caspase-3. Finally, knockdown of Mcl-1 substantially potentiated ABT-737-mediated apoptotic cell death, confirming the potency of Mcl-1 repression by NCTD in enhancing ABT-737-induced apoptosis. These results therefore suggest that combination treatment with NCTD can overcome ABT-737 resistance and enhance ABT-737 therapeutic efficacy in treating human HCC.