| Cyclin-dependent kinase inhibitor (roscovitine) suppresses growth and induces apoptosis by regulating Bcl-x in head and neck squamous cell carcinoma cells. | |
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MedLine Citation:
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PMID: 12063555 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cyclin-dependent kinases (Cdks) play essential roles in the intracellular controls of the cell cycles. Roscovitine, [2-(R)-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine], is a potent and selective inhibitor of the Cdk2 and Cdc2. We investigated whether this compound was effective against head and neck squamous cell carcinoma (HNSCC) cells. Roscovitine was found to inhibit the growth of all 11 HNSCC cell lines in time- and dose-dependent manner and to diminish the Cdk2 and Cdc2 activities. An induction of apoptosis was observed in all cells, as judged by the cell morphology, along with the appearance of cells with sub-G1 DNA contents, DNA fragmentations, and poly(ADP-ribose) polymerase (PARP) cleavage. In four HNSCC cell lines, apoptosis was induced without antecedent marked cell cycle arrest, and in the other seven cell lines, cell cycle arrest preceded cell death. We also found up-regulation of Bcl-xS in the former cell lines, and in the latter cell lines, the expressions of Bcl-2 and Bcl-xL were induced simultaneously. These results suggest that roscovitine exerts antitumor activities in HNSCC and is associated with induction of Bcl-xS. Roscovitine can be considered to provide a new chemopreventive and chemotherapeutic strategy for the clinical management of HNSCC. |
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Authors:
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Mariko Mihara; Satoru Shintani; Akihisa Kiyota; Tomohiro Matsumura; David T W Wong |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: International journal of oncology Volume: 21 ISSN: 1019-6439 ISO Abbreviation: Int. J. Oncol. Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-06-13 Completed Date: 2002-12-02 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9306042 Medline TA: Int J Oncol Country: Greece |
Other Details:
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Languages: eng Pagination: 95-101 Citation Subset: IM |
Affiliation:
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Department of Oral and Maxillofacial Surgery, Ehime University School of Medicine, Ehime 791-0295, Japan. mmariko@m.ehime-u.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects* Carcinoma, Squamous Cell / drug therapy, metabolism* Cell Cycle / drug effects Cell Division / drug effects* Cyclin-Dependent Kinases / antagonists & inhibitors*, metabolism Cyclins / metabolism Enzyme Inhibitors / pharmacology* Gene Expression Head and Neck Neoplasms / drug therapy, metabolism* Humans Proto-Oncogene Proteins c-bcl-2 / metabolism* Purines / pharmacology* Tumor Cells, Cultured / drug effects, metabolism bcl-X Protein |
| Chemical | |
Reg. No./Substance:
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0/BCL2L1 protein, human; 0/Cyclins; 0/Enzyme Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 0/Purines; 0/bcl-X Protein; 0/roscovitine; EC 2.7.11.22/Cyclin-Dependent Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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