On the Size Evolution of Gold-Monolayer-Protected Clusters by Ligand Place-Exchange Reactions: The Effect of Headgroup-Gold Interactions
Resource
LANGMUIR, 79(9), 1261-1271
Journal
LANGMUIR
Journal Volume
79
Journal Issue
9
Pages
1261-1271
Date Issued
2010
Date
2010
Author(s)
Hsieh, Cheng-Chih
Kuo, Yueh-Hsiung
Kuo, Ching-Chuan
Chen, Li-Tzong
Cheung, Chun-Hei Antonio
Chao, Tsu-Yi
Lin, Chi-Hung
Pan, Wen-Yu
Chang, Chi-Yen
Chien, Shih-Chang
Chen, Tung-Wei
Lung, Chia-Chi
Chang, Jang-Yang
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. ? 2009 Elsevier Inc. All rights reserved.
Subjects
Anticancer; Chamaecypanone C; Drug resistance; Fas/FasL; Microtubule inhibitor
SDGs
Other Subjects
antineoplastic agent; caspase 3; caspase 8; caspase 9; cell protein; chamaecypanone C; Chamaecyparis obtusa extract; cyclin B1; cyclin dependent kinase 2; epitope; Fas antigen; Fas ligand; multidrug resistance protein; plant extract; protein Cdc25C; terpene derivative; tubulin; unclassified drug; antineoplastic activity; apoptosis; article; cancer cell destruction; cell cycle arrest; cell cycle G2 phase; cell cycle M phase; cell death; Chamaecyparis obtusa; controlled study; cytotoxicity; drug binding site; drug sensitivity; flow cytometry; human; human cell; IC 50; medicinal plant; microtubule; microtubule assembly; mitochondrion; mitosis inhibition; priority journal; protein phosphorylation; Antigens, CD95; Antineoplastic Agents; Apoptosis; Bicyclo Compounds; Caspase 8; Cell Line, Tumor; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Fas Ligand Protein; Gene Expression Regulation; Humans; Microtubules; Molecular Structure
Type
journal article
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