1-(3,4-Dimethoxyphenyl)-3,5-dodecenedione (I6), a gingerdione derivative was first synthesized in our laboratory. In previous paper, several gingerdione derivatives were synthesized and found to have significant cytotoxicity against leukemia cell lines. Among them, compound I6 was the most promising one. In the present study, the mechanism of the anti- proliferative effect of I6 was investigated. Result showed that I6 induced G0/G1 arrest. RT-PCR analysis of G0/G1 arrest regulatory mRNA demonstrated that the mRNA levels of cyclin D2, cyclin E, CDK-4, and CDK-6 were decreased and P27 increased after treatment with I6. Data from DNA fragmentation analysis demonstrated that I6-induced apoptosis in human promyelocytic leukemia (HL-60) cells, and which was accompanied by upregulation of caspase-3 and Bax, and down- regulation of Bcl-2. Taken together, these results suggest that downregulation of G0/G1 associated cyclins and CDKs and upregulation of P27 may contributed I6-mediated cell cycle arrest. Furthermore, the decrease in Bcl-2 and activation of caspase-3 may be the effector mechanism through which I6 inducted apoptosis.
