title: Celecoxib-induced cytotoxic effect is potentiated by inhibition of autophagy in human urothelial carcinoma cells.
abstract: 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.
authors.affiliation: Graduate institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan ; Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Kuo-How
authors.initials: KH
authors.lastname: Huang
authors.affiliation: Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Kuan-Lin
authors.initials: KL
authors.lastname: Kuo
authors.affiliation: Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: I-Lin
authors.initials: IL
authors.lastname: Ho
authors.affiliation: Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hong-Chiang
authors.initials: HC
authors.lastname: Chang
authors.affiliation: Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yuan-Ting
authors.initials: YT
authors.lastname: Chuang
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Wei-Chou
authors.initials: WC
authors.lastname: Lin
authors.affiliation: Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ping-Yi
authors.initials: PY
authors.lastname: Lee
authors.affiliation: Department of Urology, National Taiwan University Hospital, Taipei, Taiwan ; Department of Chemical Engineering, College of Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Shih-Chen
authors.initials: SC
authors.lastname: Chang
authors.affiliation: Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chih-Kang
authors.initials: CK
authors.lastname: Chiang
authors.affiliation: Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yeong-Shiau
authors.initials: YS
authors.lastname: Pu
authors.affiliation: Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chien-Tso
authors.initials: CT
authors.lastname: Chou
authors.affiliation: Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chen-Hsun
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Graduate institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Liu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D000071193:Autophagy-Related Protein 7; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000068579:Celecoxib; D045744:Cell Line, Tumor; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D044764:Ubiquitin-Activating Enzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D018942:Macrolides; D010750:Phosphoproteins; D011720:Pyrazoles; D034741:RNA, Small Interfering; D013449:Sulfonamides; C025946:3-methyladenine; C040929:bafilomycin A1; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes; D000225:Adenine; D000068579:Celecoxib; D020123:Sirolimus