Abstract
The combretastatin A-4/oltipraz hybrid (COH), 5-(3-amino-4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-3H−1,2-dithiole-3-one (COH-203) is one of the COH compounds synthesized by our previous study, which has been reported to affect a number of cancer cell lines, such as SGC-7901, KB, HT-1080, HepG2, SMMC-7721 and BEL-7402. The sensitivity of human acute leukemia cell lines to COH-203, and the mechanism underlying its anti-proliferative effects remain unknown, which was investigated in the present study. In the present study, it was demonstrated that COH-203 had notable time- and dose-dependent antiproliferative effects on the human acute promyelocytic leukemia HL-60 cell line. Furthermore, COH-203 treatment resulted in cell cycle arrest at G2/M phase in a dose-dependent manner, and subsequently induced apoptosis. Western blot analysis revealed that upregulation of cyclin B was associated with G2/M arrest. In addition, treatment with COH-203 resulted in downregulated expression of Bcl-2. This result revealed that COH-203-induced apoptosis in HL-60 cells may occur via the mitochondrial pathway in a caspase-dependent manner.
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