|K252a induces cell cycle arrest and apoptosis by inhibiting Cdc2 and Cdc25c.|
|PMID: 10434949 Owner: NLM Status: MEDLINE|
|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.|
|L S Chin; S F Murray; P F Doherty; S K Singh|
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|Type: Journal Article|
|Title: Cancer investigation Volume: 17 ISSN: 0735-7907 ISO Abbreviation: Cancer Invest. Publication Date: 1999|
|Created Date: 1999-08-13 Completed Date: 1999-08-13 Revised Date: 2009-11-19|
Medline Journal Info:
|Nlm Unique ID: 8307154 Medline TA: Cancer Invest Country: UNITED STATES|
|Languages: eng Pagination: 391-5 Citation Subset: IM|
|Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, USA. email@example.com|
|APA/MLA Format Download EndNote Download BibTex|
CDC2 Protein Kinase / antagonists & inhibitors*, metabolism
Carbazoles / pharmacology*
Cell Cycle / drug effects*
Cell Cycle Proteins / antagonists & inhibitors*, metabolism
Cell Size / drug effects
DNA Fragmentation / drug effects
Dose-Response Relationship, Drug
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology
Histones / metabolism
Phosphorylation / drug effects
Protein Kinase Inhibitors
Protein Kinases / metabolism
Proto-Oncogene Proteins p21(ras) / metabolism
Retinoblastoma Protein / metabolism
Tumor Cells, Cultured
Up-Regulation / drug effects
|0/Carbazoles; 0/Cell Cycle Proteins; 0/Enzyme Inhibitors; 0/Histones; 0/Indole Alkaloids; 0/Protein Kinase Inhibitors; 0/Retinoblastoma Protein; 0/ras-GRF1; 97161-97-2/K 252; EC 2.7.-/Protein Kinases; EC 188.8.131.52/CDC2 Protein Kinase; EC 184.108.40.206/HRAS protein, human; EC 220.127.116.11/Proto-Oncogene Proteins p21(ras)|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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