Document Detail


Induction of apoptosis and cell-cycle arrest in human colon cancer cells by meclizine.
MedLine Citation:
PMID:  17222494     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Meclizine (MEC), a histamine H1 antagonist, is used for the treatment of motion sickness and vertigo. In this study, we demonstrate that MEC dose-dependently induced apoptosis in human colon cancer cell lines (COLO 205 and HT 29 cells). Results of a DNA ladder assay revealed that DNA ladders appeared with MEC treatment in COLO 205 cells at dosage of >50 microM. In addition, the total cell number decreased dose-dependently after treatment with MEC in COLO 205 and HT 29 cells. Using flow cytometry, the percentage of COLO 205 cells arrested at G0/G1 phase increased dose-dependently. Analysis of changes in cell-cycle arrest-associated proteins with Western blotting showed that p53 and p21 were upregulated after treatment with MEC. The kinase activities of cyclin-dependent kinase 2 (CDK2) and CDK4 were suppressed in MEC-treated cells. As for apoptosis, MEC may induce upregulation of p53 and downregulation of Bcl-2, thus causing the release of cytochrome C from mitochondria and the translocation of apoptosis-inducing factor (AIF) to the nucleus. This resulted in the activation of caspase 3, 8, and 9. Our results provide the molecular basis of MEC-induced apoptosis and cell-cycle arrest in human colon cancer cells.
Authors:
Jiunn-Chang Lin; Yuan-Soon Ho; Jie-Jen Lee; Chien-Liang Liu; Tsen-Long Yang; Chih-Hsiung Wu
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Publication Detail:
Type:  Journal Article     Date:  2006-12-09
Journal Detail:
Title:  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association     Volume:  45     ISSN:  0278-6915     ISO Abbreviation:  Food Chem. Toxicol.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-04-06     Completed Date:  2007-07-24     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8207483     Medline TA:  Food Chem Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  935-44     Citation Subset:  IM    
Affiliation:
Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Apoptosis Inducing Factor / metabolism
Blotting, Western
Cell Cycle / drug effects*
Cell Cycle Proteins / metabolism
Cell Proliferation / drug effects
Cell Survival / drug effects
Colonic Neoplasms / drug therapy*,  pathology
Cyclin-Dependent Kinases / metabolism
Cytochromes c / metabolism
DNA Fragmentation / drug effects
Dose-Response Relationship, Drug
Flow Cytometry
HT29 Cells
Histamine H1 Antagonists / pharmacology
Humans
Meclizine / pharmacology*
Chemical
Reg. No./Substance:
0/Apoptosis Inducing Factor; 0/Cell Cycle Proteins; 0/Histamine H1 Antagonists; 569-65-3/Meclizine; 9007-43-6/Cytochromes c; 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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