題名:Induction of apoptosis and cell-cycle arrest in human colon cancer cells by meclizine
作者:何元順
Jiunn-Chang Lin; Yuan-Soon Ho; Jie-Jen Lee; Chien-Liang Liu; Tsen-Long Yang; Chih-Hsiung Wu
貢獻者:醫學檢驗暨生物技術學系 上傳時間:2009-08-25T02:38:30Z
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 lM. 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
