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http://dx.doi.org/10.4062/biomolther.2007.15.3.145

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

Lee, Sang-Kwang (College of Pharmacy, Chung-Ang University)
Chae, Ah-Reum (College of Pharmacy, Chung-Ang University)
Chun, Young-Jin (College of Pharmacy, Chung-Ang University)
Publication Information
Biomolecules & Therapeutics / v.15, no.3, 2007 , pp. 145-149 More about this Journal
Abstract
We have previously shown that 2,4,3',5'-tetramethoxystilbene (TMS), a synthetic trans-stilbene analogue acting as a potent inhibitor of human cytochrome P450 1B1, induces apoptotic cell death in human cancer cells. In the present studies, we report the mechanisms of apoptotic cell death by TMS in human promyelocytic leukemic HL-60 cells. We found that treatment of HL-60 cells with TMS suppressed the cell growth in a concentration-dependent manner with $IC_{50}$ value of about 0.8 ${\mu}M$. Immunoblot experiments revealed that DMHS-induced apoptosis was associated with cleavage of poly (ADP-ribose) polymerase. The release of cytochrome c from mitochondria into the cytosol was significantly increased in response to TMS. TMS caused activation of caspase-3 in a concentration-dependent manner and TMS-mediated caspase-3 activation was partially prevented by the caspase inhibitor, zVAD-fmk. Interestingly, we found that the cytotoxic effect of anticancer drugs such as paclitaxel, docetaxel, or etoposide was enhanced in the presence of TMS. Simultaneous treatment with TCDD also significantly increased cytotoxic effects of TMS alone or TMS and anti-cancer agents. Taken together, our present results indicated that TMS leads to apoptotic cell death in HL-60 cells through activation of caspase-3 activity and release of cytochrome c into cytosol. The ability of TMS to increase cytotoxic effect of anticancer drugs may contribute to its usefulness for cancer chemotherapy.
Keywords
Tetramethoxystilbene; HL-60 cells; caspase-3; cytochrome c;
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