Document Detail


Transcriptional activation of cyclin-dependent kinase inhibitor, p21waf1 gene by treatment with a differentiation inducing agent, vesnarinone in a human salivary gland cancer cell line.
MedLine Citation:
PMID:  12725323     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recently, a new concept for cancer therapy termed "tumor dormancy therapy" has been proposed. The concept of this therapy is to prolong the survival time of cancer patients while maintaining their quality of life. We have been developing a differentiation-inducing therapy, which is included in the tumor dormancy therapy, for salivary gland cancer. In this study, we examined the effect of a differentiation-inducing drug, Vesnarinone on the growth of several cancer cells, and examined the molecular mechanism by which Vesnarinone induces the cyclin dependent kinase inhibitor, p21waf1 in the cancer cells. Vesnarinone significantly suppressed the growth of TYS (salivary gland cancer cells), PC3 (prostate cancer cells), and A431 (squamous cell cancer cells). Furthermore, Vesnarinone dose-dependently enhanced the expression of p21waf1 mRNA in TYS cells. Using the luciferase reporter assay it was found that the enhancement of p21waf1 mRNA expression by Vesnarinone was through direct transcriptional activation of the p21waf1 promoter. Thus, analyzing the molecular mechanisms of differentiation inducing drugs may lead to the development of a new therapeutic strategy for several human malignancies, including salivary gland cancer.
Authors:
F Omotehara; K Nakashiro; D Uchida; S Hino; T Fujimori; H Kawamata
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of experimental & clinical cancer research : CR     Volume:  22     ISSN:  0392-9078     ISO Abbreviation:  J. Exp. Clin. Cancer Res.     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-05-02     Completed Date:  2004-01-06     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8308647     Medline TA:  J Exp Clin Cancer Res     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  57-60     Citation Subset:  IM    
Affiliation:
Dept. of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Mibu, Shimo-tsuga, Tochigi, Japan.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / therapeutic use*
Cell Differentiation / drug effects
Cell Division / drug effects
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinases / genetics
Cyclins / genetics*
Enzyme Inhibitors
Gene Expression Regulation, Neoplastic / drug effects*
Humans
Plasmids
Quinolines / therapeutic use*
RNA, Messenger / genetics
Salivary Gland Neoplasms / drug therapy,  pathology*
Transcriptional Activation*
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Enzyme Inhibitors; 0/Quinolines; 0/RNA, Messenger; 81840-15-5/vesnarinone; 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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