Document Detail

Effect of arsenic trioxide on cell cycle arrest in head and neck cancer cell line PCI-1.
MedLine Citation:
PMID:  10558879     Owner:  NLM     Status:  MEDLINE    
Arsenic trioxide (As(2)O(3)) has been shown to inhibit the proliferation of hematologic malignant cells. However, little is known about the effect of As(2)O(3) on solid tumor. In this study, we investigated the antitumoral effect of As(2)O(3) on head and neck cancer cell lines in vitro. Treatment of As(2)O(3) inhibited the proliferation of all of 4 cell lines examined in a dose-dependent manner. To address the mechanism of antitumoral effect of As(2)O(3), cell cycle analysis was attempted in As(2)O(3)-most sensitive PCI-1 cells. Treatment of As(2)O(3) (2 microM) induced efficiently G2/M arrest in PCI-1 cells following 3 days of exposure. During the G2/M arrest, cyclin-dependent kinase inhibitor, p21, was increased in a time-dependent manner. Analysis of cell cycle regulatory proteins demonstrated that As(2)O(3) (2 microM) did not change the steady-state levels of CDK2, CDK4, CDK6, cyclin D1, cyclin E and cyclin A, but decreased the protein levels of cdc2 and cyclin B1. Furthermore, treatment of As(2)O(3) markedly enhanced the binding of p21 with cdc2, and the activity of cdc2 kinase was decreased in a time-dependent manner. These results suggest that As(2)O(3) inhibits the proliferation of head and neck cancer cells via G2/M arrest in association with the induction of p21 and the reduction of cdc2 kinase activity.
J G Seol; W H Park; E S Kim; C W Jung; J M Hyun; B K Kim; Y Y Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  265     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  1999 Nov 
Date Detail:
Created Date:  1999-12-20     Completed Date:  1999-12-20     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  400-4     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Academic Press.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 110-744, Korea.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Arsenicals / pharmacology*
CDC2 Protein Kinase / metabolism
Cell Cycle / drug effects*
Cell Division / drug effects
Cyclin B / metabolism
Cyclin B1
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / metabolism
G2 Phase / drug effects
Growth Inhibitors / pharmacology
Head and Neck Neoplasms / drug therapy*,  metabolism,  pathology
Mitosis / drug effects
Oxides / pharmacology*
Tumor Cells, Cultured
Reg. No./Substance:
0/Antineoplastic Agents; 0/Arsenicals; 0/CCNB1 protein, human; 0/CDKN1A protein, human; 0/Cyclin B; 0/Cyclin B1; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Growth Inhibitors; 0/Oxides; 1327-53-3/arsenic trioxide; EC Protein Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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