Cyclin-dependent kinase inhibitors block proliferation of human gastric cancer cells.
BACKGROUND
Olomoucine and roscovitine are novel compounds that are designed to inhibit cyclin-dependent kinases (e.g., Cdk2 and cdc2). Cdks regulate progression through key checkpoints of the cell cycle. The purpose of this study was to determine (1) whether olomoucine and roscovitine inhibit Cdk2 and cdc2 kinase activities of the human gastric cancer cell line SIIA and (2) whether olomoucine and roscovitine block cell proliferation and cell cycle progression.


METHODS
SIIA cells were treated with olomoucine or roscovitine and examined for Cdk2 and cdc2 activities by using histone H1 as the substrate. Cell numbers were counted with a Coulter counter. Cell cycle distribution was analyzed by DNA flow cytometry.


RESULTS
Olomoucine and roscovitine completely blocked Cdk2 and cdc2 activities in SIIA cells. Both compounds were also able to inhibit proliferation of SIIA cells, as well as three other human gastric cancer cell lines (AGS, MKN45-630, and SNU-1). Cell cycle analysis showed that treatment with olomoucine or roscovitine for 24 hours led to a decrease in the S phase population and an increase in the G2/M population.


CONCLUSIONS
We have shown that Cdk inhibitors, olomoucine and roscovitine, are a new class of antineoplastic molecules with potential therapeutic benefits for gastric cancers.
Iseki
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Department of Surgery, University of Texas Medical Branch, Galveston 77555-0542, USA.
Ko
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TC
Xue
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Seapan
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A
Hellmich
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MR
Townsend
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CM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors*; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007701:Kinetin; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011687:Purines / Q000494:pharmacology*; D000077546:Roscovitine; D013274:Stomach Neoplasms; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006657:Histones; D011687:Purines; D000077546:Roscovitine; C090046:olomoucine; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D007701:Kinetin