Chamaecypanone C, a novel skeleton microtubule inhibitor, with anticancer activity by trigger caspase 8-Fas/FasL dependent apoptotic pathway in human cancer cells

Cheng Chih Hsieh, Yueh Hsiung Kuo, Ching Chuan Kuo, Li Tzong Chen, Chun-Hei Cheung, Tsu Yi Chao, Chi Hung Lin, Wen Yu Pan, Chi Yen Chang, Shih Chang Chien, Tung Wei Chen, Chia Chi Lung, Jang-Yang Chang

研究成果: Article

24 引文 斯高帕斯(Scopus)

摘要

Microtubule is a popular target for anticancer drugs. Chamaecypanone C, is a natural occurring novel skeleton compound isolated from the heartwood of Chamaecyparis obtusa var. formosana. The present study demonstrates that chamaecypanone C induced mitotic arrest through binding to the colchicine-binding site of tubulin, thus preventing tubulin polymerization. In addition, cytotoxic activity of chamaecypanone C in a variety of human tumor cell lines has been ascertained, with IC50 values in nanomolar ranges. Flow cytometric analysis revealed that chamaecypanone C treated human KB cancer cells were arrested in G2-M phases in a time-dependent manner before cell death occurred. Additional studies indicated that the effect of Chamaecypanone C on cell cycle arrest was associated with an increase in cyclin B1 levels and a mobility shift of Cdc2/Cdc25C. The changes in Cdc2 and Cdc25C coincided with the appearance of phosphoepitopes recognized by a marker of mitosis, MPM-2. Interestingly, this compound induced apoptotic cell death through caspase 8-Fas/FasL dependent pathway, instead of mitochondria/caspase 9-dependent pathway. Notably, several KB-derived multidrug resistant cancer cell lines overexpressing P-gp170/MDR and MRP were sensitive to Chamaecypanone C. Taken together, these findings indicated that Chamaecypanone C is a promising anticancer compound that has potential for management of various malignancies, particularly for patients with drug resistance.

原文English
頁(從 - 到)1261-1271
頁數11
期刊Biochemical Pharmacology
79
發行號9
DOIs
出版狀態Published - 2010 五月 1

    指紋

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

引用此

Hsieh, C. C., Kuo, Y. H., Kuo, C. C., Chen, L. T., Cheung, C-H., Chao, T. Y., Lin, C. H., Pan, W. Y., Chang, C. Y., Chien, S. C., Chen, T. W., Lung, C. C., & Chang, J-Y. (2010). Chamaecypanone C, a novel skeleton microtubule inhibitor, with anticancer activity by trigger caspase 8-Fas/FasL dependent apoptotic pathway in human cancer cells. Biochemical Pharmacology, 79(9), 1261-1271. https://doi.org/10.1016/j.bcp.2009.12.017