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 Antonio 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

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25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1261-1271
Number of pages11
JournalBiochemical Pharmacology
Volume79
Issue number9
DOIs
Publication statusPublished - 2010 May 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

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