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

Research output: Contribution to journalArticle

24 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

Fingerprint

Caspase 8
Skeleton
Microtubules
Cells
Neoplasms
Cell death
Tubulin
Chamaecyparis
Cell Death
Cyclin B1
KB Cells
Mitochondria
Caspase 9
G2 Phase
Colchicine
Cell Cycle Checkpoints
chamaecypanone C
Tumor Cell Line
Mitosis
Drug Resistance

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

Hsieh, Cheng Chih ; Kuo, Yueh Hsiung ; Kuo, Ching Chuan ; Chen, Li Tzong ; Cheung, Chun-Hei ; Chao, Tsu Yi ; Lin, Chi Hung ; Pan, Wen Yu ; Chang, Chi Yen ; Chien, Shih Chang ; Chen, Tung Wei ; Lung, Chia Chi ; Chang, Jang-Yang. / Chamaecypanone C, a novel skeleton microtubule inhibitor, with anticancer activity by trigger caspase 8-Fas/FasL dependent apoptotic pathway in human cancer cells. In: Biochemical Pharmacology. 2010 ; Vol. 79, No. 9. pp. 1261-1271.
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Chamaecypanone C, a novel skeleton microtubule inhibitor, with anticancer activity by trigger caspase 8-Fas/FasL dependent apoptotic pathway in human cancer cells. / Hsieh, Cheng Chih; Kuo, Yueh Hsiung; Kuo, Ching Chuan; Chen, Li Tzong; Cheung, Chun-Hei; Chao, Tsu Yi; Lin, Chi Hung; Pan, Wen Yu; Chang, Chi Yen; Chien, Shih Chang; Chen, Tung Wei; Lung, Chia Chi; Chang, Jang-Yang.

In: Biochemical Pharmacology, Vol. 79, No. 9, 01.05.2010, p. 1261-1271.

Research output: Contribution to journalArticle

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AU - Hsieh, Cheng Chih

AU - Kuo, Yueh Hsiung

AU - Kuo, Ching Chuan

AU - Chen, Li Tzong

AU - Cheung, Chun-Hei

AU - Chao, Tsu Yi

AU - Lin, Chi Hung

AU - Pan, Wen Yu

AU - Chang, Chi Yen

AU - Chien, Shih Chang

AU - Chen, Tung Wei

AU - Lung, Chia Chi

AU - Chang, Jang-Yang

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