CDK inhibitors suppress apoptosis induced by chemicals and by excessive expression of a cell death gene, reaper, in Drosophila cells

The present study was aimed to investigate whether or not cyclin-dependent kinases (CDKs) participate in different cascades leading to apoptosis. We e xamined the effects of two CDK inhibitors, olomoucine (OLM) and buty-rolact one-I (BL-I), on apoptosis induced in two kinds of Drosophila cell lines. I ncreases of caspase activity induced by actinomycin D, cycloheximide, H-7 o r A23187 in a Drosophila neuronal cell line, ML-DmBG2-c2, and induced by ex cessive expression of a Drosophila cell death gene, reaper, in Drosophila S 2 cells were suppressed by 24-h pretreatment of each CDK inhibitor. Concomi tant with the suppression of the caspase activity, fragmentations of cells and DNA, representatives of apoptosis, were also inhibited. These results s uggest that CDK(s) participates in progression of apoptosis. However, these effects of the CDK inhibitors were also observed even at lower doses which did not affect cell proliferation. Therefore, it was shown that apoptosis is not always related to cell cycle in Drosophila cells. It was also sugges ted that the target(s) of the CDK inhibitors locates upstream of caspase in the cascade(s) of apoptosis.