title: Celecoxib induces apoptosis via a mitochondria‑dependent pathway in the H22 mouse hepatoma cell line.
abstract: Celecoxib is a potent nonsteroidal anti-inflammatory drug that has demonstrated promise in cancer chemoprevention and treatment. The present study was conducted to gain insight into the molecular mechanism by which celecoxib induces apoptosis in the H22 mouse hepatoma cell line. The effect of celecoxib on the viability of H22 mouse hepatoma cells was assessed with sulforhodamine B assay. Apoptosis and mitochondrial membrane potential were detected by a flow cytometric assay. The protein expression levels of Bax, Bcl‑2, cytochrome c, caspase-3, caspase-9, apoptosis-inducing factor (AIF), peroxisome proliferator-activated receptor (PPAR)γ and nuclear factor (NF)-κB were determined by western blot analysis. The data demonstrated that celecoxib reduced the percentage of viable H22 cells in a dose- and time-dependent manner, which was associated with cell apoptosis. Furthermore, celecoxib induced apoptosis via the loss of the mitochondrial transmembrane potential (ΔΨm), the release of cytochrome c and AIF, and the activation of caspase-9 and caspase-3. Celecoxib also increased the abundance of the pro-apoptotic protein Bax and reduced the levels of the anti-apoptotic protein Bcl-2. The data demonstrated that celecoxib induced apoptosis in mouse liver cancer cells via the mitochondria-dependent pathway rather than the PPARγ/NF-κB signaling pathway, which indicates that celecoxib may be an effective agent in the clinical management of hepatocellular carcinoma.
authors.affiliation: Department of Pharmacology and Biochemistry, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Shao
authors.affiliation: Department of Pharmacology and Biochemistry, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Mujie
authors.initials: M
authors.lastname: Kan
authors.affiliation: Department of Pharmacology and Biochemistry, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Qiao
authors.affiliation: Department of Pharmacology and Biochemistry, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Pharmacology and Biochemistry, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Biochemistry, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Xuanang
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Pharmacology and Biochemistry, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Biochemistry, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D000068579:Celecoxib; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011720:Pyrazoles / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D011720:Pyrazoles; D013449:Sulfonamides; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9; D000068579:Celecoxib