Abstract
Cyclin dependent kinases propel the cell cycle in collaboration with cyclins. We have examined the expression of cdk2/cdc2 in adenoma and focal carcinoma in adenomatous tissue to explore their role in tumorigenesis of colorectum. Immunohistochemical study revealed that cdk2/cdc2 was overexpressed in a subsets of adenoma (14/50; 28.0%) but this overexpression was much more obvious in focal carcinoma (13/15; 86.7%). These results suggest that cdk2/cdc2 is remarkably upregulated together with a malignant change. In an effort to demonstrate a significant role for cdk2/cdc2 in colon cancer, we investigated growth and apoptosis with butyrolactone I, a specific inhibitor for cdk2/cdc2, using 4 colon carcinoma cell lines (HCT116, LoVo, HT29, Colo 320DM). Butyrolactone I inhibited proliferation of all colon carcinoma cell lines at 100 microM and it induced apoptosis in LoVo cell line with induction of p53. Our findings suggest that inhibition of cdk2/cdc2 may be a useful strategy against colon cancer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4-Butyrolactone / analogs & derivatives*
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4-Butyrolactone / pharmacology
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Adenoma / enzymology
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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CDC2 Protein Kinase / antagonists & inhibitors*
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CDC2 Protein Kinase / biosynthesis*
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CDC2-CDC28 Kinases*
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Carcinoma / enzymology
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Cell Division / drug effects
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Colonic Neoplasms / drug therapy*
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Colonic Neoplasms / enzymology*
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Colonic Neoplasms / pathology
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases / antagonists & inhibitors*
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Cyclin-Dependent Kinases / biosynthesis*
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Enzyme Inhibitors / pharmacology*
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Humans
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / biosynthesis*
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Tumor Cells, Cultured / drug effects
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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butyrolactone I
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Protein Serine-Threonine Kinases
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CDC2 Protein Kinase
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CDC2-CDC28 Kinases
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CDK2 protein, human
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases
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4-Butyrolactone