Document Detail


Cyclin-dependent kinase inhibitor (roscovitine) suppresses growth and induces apoptosis by regulating Bcl-x in head and neck squamous cell carcinoma cells.
MedLine Citation:
PMID:  12063555     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Mariko Mihara; Satoru Shintani; Akihisa Kiyota; Tomohiro Matsumura; David T W Wong
Related Documents :
8282815 - Interleukin-10 prevents spontaneous death of germinal center b cells by induction of th...
15105045 - Potentiated anticancer effects on hepatoma cells by the retinoid adapalene.
10229685 - Protection against hydrogen peroxide cytotoxicity in rat-1 fibroblasts provided by the ...
10471445 - Inflammatory responses in the cerebral cortex after ischemia in the p7 neonatal rat.
22177215 - Histochemical analysis of glycoproteins in the gill epithelium of an indian major carp,...
21193455 - Nanoliposomal ceramide prevents in vivo growth of hepatocellular carcinoma.
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of oncology     Volume:  21     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-06-13     Completed Date:  2002-12-02     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  95-101     Citation Subset:  IM    
Affiliation:
Department of Oral and Maxillofacial Surgery, Ehime University School of Medicine, Ehime 791-0295, Japan. mmariko@m.ehime-u.ac.jp
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Apoptosis / 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:
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


Previous Document:  Human tumor cell infection by Newcastle Disease Virus leads to upregulation of HLA and cell adhesion...
Next Document:  Effects of hyperglycemia on oxygenation, radiosensitivity and bioenergetic status of subcutaneous RI...