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 examined the effects of two CDK inhibitors, olomoucine (OLM) and butyrolactone-I (BL-I), on apoptosis induced in two kinds of Drosophila cell lines. Increases of caspase activity induced by actinomycin D, cycloheximide, H-7 or A23187 in a Drosophila neuronal cell line, ML-DmBG2-c2, and induced by excessive expression of a Drosophila cell death gene, reaper, in Drosophila S2 cells were suppressed by 24-h pretreatment of each CDK inhibitor. Concomitant with the suppression of the caspase activity, fragmentations of cells and DNA, representatives of apoptosis, were also inhibited. These results suggest 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 suggested that the target(s) of the CDK inhibitors locates upstream of caspase in the cascade(s) of apoptosis.
Nagano
M
M
Department of Pharmacology, Nippon Medical School, Tokyo, Japan.
Ui-Tei
K
K
Suzuki
H
H
Piao
Z
Z
Miyata
Y
Y
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D007701:Kinetin; D010455:Peptides / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011687:Purines / Q000494:pharmacology; D013997:Time Factors
D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D010455:Peptides; D011687:Purines; C086973:rpr protein, Drosophila; C090046:olomoucine; C082868:butyrolactone I; D018844:Cyclin-Dependent Kinases; D015107:4-Butyrolactone; D007701:Kinetin