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

doi:10.1016/j.bcp.2009.12.017

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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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 language	English
Pages (from-to)	1261-1271
Number of pages	11
Journal	Biochemical Pharmacology
Volume	79
Issue number	9
DOIs	https://doi.org/10.1016/j.bcp.2009.12.017
Publication status	Published - 2010 May 1

All Science Journal Classification (ASJC) codes

Biochemistry
Pharmacology

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10.1016/j.bcp.2009.12.017

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Hsieh, C. C., Kuo, Y. H., Kuo, C. C., Chen, L. T., Cheung, C. H. A., 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

@article{c46027fdcebc41d8adc23ea7fcba3f18,

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

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.",

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

note = "Funding Information: This work was supported in part by grants from National Health Research Institutes , Taipei, Taiwan (NHRI intramural grant CA-098-PP-02 ), the National Science Council , Taipei, Taiwan (NSC 98-2323-B-400-004 ), and China Medical University , Taichung, Taiwan (CMU98-CT-01) .",

year = "2010",

month = may,

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doi = "10.1016/j.bcp.2009.12.017",

language = "English",

volume = "79",

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journal = "Biochemical Pharmacology",

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Hsieh, CC, Kuo, YH, Kuo, CC, Chen, LT, Cheung, CHA, Chao, TY, Lin, CH, Pan, WY, Chang, CY, Chien, SC, Chen, TW, Lung, CC & Chang, JY 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, vol. 79, no. 9, pp. 1261-1271. https://doi.org/10.1016/j.bcp.2009.12.017

TY - JOUR

T1 - Chamaecypanone C, a novel skeleton microtubule inhibitor, with anticancer activity by trigger caspase 8-Fas/FasL dependent apoptotic pathway in human cancer cells

AU - Hsieh, Cheng Chih

AU - Kuo, Yueh Hsiung

AU - Kuo, Ching Chuan

AU - Chen, Li Tzong

AU - Cheung, Chun Hei Antonio

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

N1 - Funding Information: This work was supported in part by grants from National Health Research Institutes , Taipei, Taiwan (NHRI intramural grant CA-098-PP-02 ), the National Science Council , Taipei, Taiwan (NSC 98-2323-B-400-004 ), and China Medical University , Taichung, Taiwan (CMU98-CT-01) .

PY - 2010/5/1

Y1 - 2010/5/1

N2 - 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.

AB - 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.

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DO - 10.1016/j.bcp.2009.12.017

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AN - SCOPUS:77649191492

SN - 0006-2952

VL - 79

SP - 1261

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JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

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ER -

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

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