Tubulozole-induced G2/M cell cycle arrest in human colon cancer cells through formation of microtubule polymerization mediated by ERK1/2 and Chk1 kinase activation

Yean Hwei Chou, Yuan Soon Ho, Chi-Cheng Wu, Chiah Yang Chai, Soul-Chin Chen, Chia Hwa Lee, Pei Shan Tsai, Chih Hsiung Wu

研究成果: 雜誌貢獻文章

19 引文 斯高帕斯(Scopus)

摘要

Our studies demonstrated that human colon cancer cells (COLO 205), with higher expression level of check point kinase 1 (Chk1), were more sensitive to microtubule damage agent Tubulozole (TUBU) induced G2/M phase arrest than normal human colon epithelial (CRL) cells. TUBU (10 μM, for 3 h) treatment resulted in rapid and sustained phosphorylation of Cdc25C (Ser-216) leading to increased 14-3-3β binding. This resulted in increased nuclear translocation. In addition, TUBU induced phosphorylation of the Cdc25C (Ser-216) and Bad (Ser-155) proteins were blocked by Chk1 SiRNA-transfection. Surprisingly, cellular apotosis was observed in cells treated with TUBU after Chk1 SiRNA inhibition. We further demonstrated that extracellular signal-regulated kinase (ERK) activation by TUBU was needed for Chk1 kinase activation and microtubule formation as shown by the attenuation of these responses by the ERK1/2 specific inhibitor PD98059. However, TUBU induced ERK1/2 phosphorylation was not blocked in the Chk1 SiRNA-transfected COLO 205 cells. These results imply that ERK1/2 mediated Chk1 activation may be play an important role in determining TUBU induced G2/M arrest or apoptosis in COLO 205 cells.
原文英語
頁(從 - 到)1356-1367
頁數12
期刊Food and Chemical Toxicology
45
發行號8
DOIs
出版狀態已發佈 - 八月 2007

ASJC Scopus subject areas

  • Food Science
  • Toxicology

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