Celecoxib-induced cytotoxic effect is potentiated by inhibition of autophagy in human urothelial carcinoma cells

Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, can elicit anti-tumor effects in various malignancies. Here, we sought to clarify the role of autophagy in celecoxib-induced cytotoxicity in human urothelial carcinoma (UC) cells. The results shows celecoxib induced cellular stress response such as en...

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Veröffentlicht in:	PloS one 2013-12, Vol.8 (12), p.e82034
Hauptverfasser:	Huang, Kuo-How, Kuo, Kuan-Lin, Ho, I-Lin, Chang, Hong-Chiang, Chuang, Yuan-Ting, Lin, Wei-Chou, Lee, Ping-Yi, Chang, Shih-Chen, Chiang, Chih-Kang, Pu, Yeong-Shiau, Chou, Chien-Tso, Hsu, Chen-Hsun, Liu, Shing-Hwa
Format:	Artikel
Sprache:	eng
Schlagworte:	Adenine - analogs & derivatives Adenine - pharmacology Angiogenesis inhibitors Anticancer properties Antineoplastic Agents - pharmacology Apoptosis Autophagy Autophagy - drug effects Autophagy-Related Protein 7 Bladder Bladder cancer c-Jun protein Cancer therapies Carcinoma Carcinoma, Transitional Cell - drug therapy Carcinoma, Transitional Cell - genetics Carcinoma, Transitional Cell - metabolism Carcinoma, Transitional Cell - pathology Celecoxib Cell culture Cell cycle Cell death Cell Line, Tumor Cellular stress response Chemotherapy COX-2 inhibitors Cyclooxygenase 2 Inhibitors - pharmacology Cyclooxygenase-2 Cytotoxicity Endoplasmic reticulum Endoplasmic Reticulum Stress - drug effects Flow cytometry Gene Expression Regulation, Neoplastic Hospitals Humans Immunoglobulins Inflammation Inhibition Insurance claims JNK Mitogen-Activated Protein Kinases - genetics JNK Mitogen-Activated Protein Kinases - metabolism Kinases Macrolides - pharmacology MAP Kinase Kinase 4 - genetics MAP Kinase Kinase 4 - metabolism Membranes Metastasis Phagocytosis Phosphoproteins - genetics Phosphoproteins - metabolism Proteins Pyrazoles - pharmacology Rapamycin RNA, Small Interfering - genetics RNA, Small Interfering - metabolism Rodents Signal Transduction Sirolimus - pharmacology Sulfonamides - pharmacology Toxicity Toxicology Transcription factors Transfection Ubiquitin-Activating Enzymes - antagonists & inhibitors Ubiquitin-Activating Enzymes - genetics Ubiquitin-Activating Enzymes - metabolism Urinary Bladder Neoplasms - drug therapy Urinary Bladder Neoplasms - genetics Urinary Bladder Neoplasms - metabolism Urinary Bladder Neoplasms - pathology Urology Urothelial carcinoma Yeast
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Beschreibung
Zusammenfassung:	Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, can elicit anti-tumor effects in various malignancies. Here, we sought to clarify the role of autophagy in celecoxib-induced cytotoxicity in human urothelial carcinoma (UC) cells. The results shows celecoxib induced cellular stress response such as endoplasmic reticulum (ER) stress, phosopho-SAPK/JNK, and phosopho-c-Jun as well as autophagosome formation in UC cells. Inhibition of autophagy by 3-methyladenine (3-MA), bafilomycin A1 or ATG7 knockdown potentiated celecoxib-induced apoptosis. Up-regulation of autophagy by rapamycin or GFP-LC3B-transfection alleviated celecoxib-induced cytotoxicity in UC cells. Taken together, the inhibition of autophagy enhances therapeutic efficacy of celecoxib in UC cells, suggesting a novel therapeutic strategy against UC.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0082034