K252a induces cell cycle arrest and apoptosis by inhibiting Cdc2 and Cdc25c.
The indole carbazole K252a has been shown in previous studies to inhibit the platelet-derived growth factor signal transduction pathway in gliomas. Because K252a has nonspecific effects on protein kinase function, we studied its effect on cyclin-dependent kinases (CDK) and cell cycle blockade in glioma cells. K252a blocked T98G cells at the G1/S and G2/M checkpoints. Consistent with cell cycle arrest, K252a was shown to hypophosphorylate Rb, upregulate p21, and decrease Cdc2 and Cdc25c activity. Finally, cell cycle arrest in T98G cells resulted in apoptosis as determined by cell morphology and DNA laddering. K252a is a useful tool for studying the effects of CDK inhibition and cell cycle blockade in tumor cells.
Chin
L S
LS
Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, USA. lchin@surgery1.umaryland.edu
Murray
S F
SF
Doherty
P F
PF
Singh
S K
SK
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D005910:Glioma; D006657:Histones / Q000378:metabolism; D006801:Humans; D026121:Indole Alkaloids; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects; D020666:ras-GRF1
D002227:Carbazoles; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D006657:Histones; D026121:Indole Alkaloids; D047428:Protein Kinase Inhibitors; D016160:Retinoblastoma Protein; D020666:ras-GRF1; C049985:staurosporine aglycone; D011494:Protein Kinases; D016203:CDC2 Protein Kinase; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)