Celecoxib induces apoptosis via a mitochondria‑dependent pathway in the H22 mouse hepatoma cell line

Shao,Dan; Kan,Mujie; Qiao,Ping; Pan,Yue; Wang,Zheng; Xiao,Xuanang; Li,Jing; Chen,Li

doi:10.3892/mmr.2014.2461

Celecoxib induces apoptosis via a mitochondria‑dependent pathway in the H22 mouse hepatoma cell line

Authors:
- Dan Shao
- Mujie Kan
- Ping Qiao
- Yue Pan
- Zheng Wang
- Xuanang Xiao
- Jing Li
- Li Chen
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Affiliations: Department of Pharmacology and Biochemistry, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: August 7, 2014 https://doi.org/10.3892/mmr.2014.2461
Pages: 2093-2098

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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.

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