Mechanism of Apoptotic Cell Death by 2,4,3',5'-Tetramethoxystilbene in Human Promyelocytic Leukemic HL-60 Cells

Abstract

trans-stilbene ana-logue acting as a potent inhibitor of human cytochrome P450 1B1, induces apoptotic cel death in human cancercells. In the present studies, we report the mechanisms of apoptotic cell death by TMS in human promyelocyticleukemic HL-60 cels. We found that treatment of HL-60 cels with TMS suppresed the cel growth in a con-centration-dependent manner with IC50 value of about 0.8 .M. Imunoblot experiments revealed that DMHS-cfrom mitochondria into the cytosol was significantly increased in response to TMS. TMS caused activation ofcaspase-3 in a concentration-dependent manner and TMS-mediated caspase-3 activation was partially preventedby the caspase inhibitor, zVAD-fmk. Interestingly, we found that the cytoxic efect of anticancer drugs such aspaclitaxel, docetaxel, or etoposide was enhanced in the presence of TMS. Simultaneous treatment with TCDDpresent results indicated that TMS leads to apoptotic cell death in HL-60 cels through activation of caspase-3activity and release of cytochrome c into cytosol. The ability of TMS to increase cytotoxic effect of anticancerdrugs may contribute to its usefulness for cancer chemotherapy.Keywords . Tetramethoxystilbene, HL-60 cells, caspase-3, cytochrome c