Celecoxib-induced cytotoxic effect is potentiated by inhibition of autophagy in human urothelial carcinoma cells
Journal
PLoS ONE
Journal Volume
8
Journal Issue
12
Pages
e82034
Date Issued
2013
Author(s)
Kuo K.-L.
Ho I.-L.
Chuang Y.-T.
Lee P.-Y.
Chang S.-C.
Chou C.-T.
Hsu C.-H.
Liu S.-H.
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-LC3Btransfection 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. Copyright: ? 2013 Huang et al.
SDGs
Other Subjects
3 methyladenine; autophagy protein 5; bafilomycin A1; celecoxib; cyclooxygenase 2; green fluorescent protein; Janus kinase; mammalian target of rapamycin inhibitor; mitogen activated protein kinase; phosphatidylinositol 3 kinase; rapamycin; small interfering RNA; stress activated protein kinase; antineoplastic activity; apoptosis; article; autophagosome; autophagy; cancer cell culture; cell culture; cell viability; controlled study; drug cytotoxicity; endoplasmic reticulum stress; enzyme inhibition; flow cytometry; human; human cell; transitional cell carcinoma; upregulation; Adenine; Antineoplastic Agents; Autophagy; Carcinoma, Transitional Cell; Cell Line, Tumor; Cyclooxygenase 2 Inhibitors; Endoplasmic Reticulum Stress; Gene Expression Regulation, Neoplastic; Humans; JNK Mitogen-Activated Protein Kinases; Macrolides; MAP Kinase Kinase 4; Phosphoproteins; Pyrazoles; RNA, Small Interfering; Signal Transduction; Sirolimus; Sulfonamides; Ubiquitin-Activating Enzymes; Urinary Bladder Neoplasms
Type
journal article