Induction of apoptosis and cell-cycle arrest in human colon cancer cells by meclizine

Jiunn Chang Lin, Yuan Soon Ho, Jie Jen Lee, Chien Liang Liu, Tsen Long Yang, Chih Hsiung Wu

研究成果: 雜誌貢獻文章

24 引文 (Scopus)

摘要

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 μM. 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.

原文英語
頁(從 - 到)935-944
頁數10
期刊Food and Chemical Toxicology
45
發行號6
DOIs
出版狀態已發佈 - 六月 2007

指紋

Meclizine
Cell Cycle Checkpoints
colorectal neoplasms
Colonic Neoplasms
apoptosis
Cells
Apoptosis
ladders
cells
dosage
HT29 Cells
Ladders
cyclin-dependent kinase
DNA
caspase-3
Cyclin-Dependent Kinase 2
Apoptosis Inducing Factor
Histamine H1 Antagonists
cytochromes
histamine

ASJC Scopus subject areas

  • Food Science
  • Toxicology

引用此文

Induction of apoptosis and cell-cycle arrest in human colon cancer cells by meclizine. / Lin, Jiunn Chang; Ho, Yuan Soon; Lee, Jie Jen; Liu, Chien Liang; Yang, Tsen Long; Wu, Chih Hsiung.

於: Food and Chemical Toxicology, 卷 45, 編號 6, 06.2007, p. 935-944.

研究成果: 雜誌貢獻文章

Lin, Jiunn Chang ; Ho, Yuan Soon ; Lee, Jie Jen ; Liu, Chien Liang ; Yang, Tsen Long ; Wu, Chih Hsiung. / Induction of apoptosis and cell-cycle arrest in human colon cancer cells by meclizine. 於: Food and Chemical Toxicology. 2007 ; 卷 45, 編號 6. 頁 935-944.
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