XIAP-mediated protection of H460 lung cancer cells against cisplatin

Molecular mechanism(s) responsible for drug resistance of non-small cell lung cancer (NSCLC) cells to cisplatin was investigated. Results showed that cisplatin (50 μM)-induced cell death (apoptosis) was more significant in CH27 and A549 cell lines than in H460. The high protein levels of X-linked in...

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Bibliographic Details
Published in:European journal of pharmacology 2010-02, Vol.627 (1), p.75-84
Main Authors: Cheng, Yow-Jyun, Jiang, Hang-Shiang, Hsu, Shih-Lan, Lin, Li-Chiung, Wu, Chieh-Liang, Ghanta, Vithal K., Hsueh, Chi-Mei
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Benzoquinones - pharmacology
Biological and medical sciences
Carcinoma, Non-Small-Cell Lung - pathology
Caspase 3
Caspase 3 - metabolism
Cell Line, Tumor
Cisplatin
Cisplatin - pharmacology
Cytochromes c - metabolism
Dose-Response Relationship, Drug
Drug resistance
Drug Resistance, Neoplasm - drug effects
Gene Knockdown Techniques
Humans
Lung Neoplasms - pathology
Medical sciences
Membrane Potential, Mitochondrial - drug effects
Mitochondria - drug effects
Mitochondria - metabolism
NSCLC
Pharmacology. Drug treatments
Pneumology
RNA, Small Interfering - genetics
Time Factors
Tumors of the respiratory system and mediastinum
X-Linked Inhibitor of Apoptosis Protein - antagonists & inhibitors
X-Linked Inhibitor of Apoptosis Protein - deficiency
X-Linked Inhibitor of Apoptosis Protein - genetics
X-Linked Inhibitor of Apoptosis Protein - metabolism
XIAP
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Summary:Molecular mechanism(s) responsible for drug resistance of non-small cell lung cancer (NSCLC) cells to cisplatin was investigated. Results showed that cisplatin (50 μM)-induced cell death (apoptosis) was more significant in CH27 and A549 cell lines than in H460. The high protein levels of X-linked inhibitor-of-apoptosis protein (XIAP) observed in H460 cells appeared to play a key role in the regulation of cisplatin resistance of H460 cells. XIAP can bind to and suppress the activities of caspase 3 in H460 cells and lead to apoptosis inhibition of these cells. Blockade of XIAP activity by Embelin (XIAP inhibitor) or siRNA has increased caspase 3 activities and promoted cisplatin-induced cell death of H460 cells. The results indicate a therapeutic value of Embelin and/or XIAP siRNA in the control of cisplatin-resistant NSCLC cells (H460).
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2009.11.003