Ursolic acid induces apoptosis via Akt/NF-κB signaling suppression in T24 human bladder cancer cells

Gai,Long; Cai,Na; Wang,Lingling; Xu,Xiaoyi; Kong,Xiangbo

doi:10.3892/mmr.2013.1364

Ursolic acid induces apoptosis via Akt/NF-κB signaling suppression in T24 human bladder cancer cells

Authors:
- Long Gai
- Na Cai
- Lingling Wang
- Xiaoyi Xu
- Xiangbo Kong
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Affiliations: Department of Urologic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 13003, P.R. China, Department of Respiratory Medicine, Haerbin No.1 Hospital, Harbin, Heilongjiang 150000, P.R. China, Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Hematology and Oncology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: March 11, 2013 https://doi.org/10.3892/mmr.2013.1364
Pages: 1673-1677

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Abstract

The Akt/NF-κB pathway is involved in numerous anti‑apoptotic and drug resistance events which occur in various types of bladder cancer. The present study investigated the role of ursolic acid in the regulation of anti-apoptotic Akt and NF-κBp65 signaling. T24 human bladder cancer cells were treated with ursolic acid at final concentrations of 12.5, 25 or 50 µmol/l for 48 h. Quantitative PCR (qPCR) and western blotting were performed to detect mRNA and protein expression, respectively. The results showed that anti-apoptotic phospho-Akt1 (pAkt1), phospho-IκBα (pIκBα), NF-κBp65 and Bcl-2 were inhibited and pro-apoptotic caspase-3 was upregulated in a dose‑dependent manner. A 50 µmol/l dose of ursonic acid decreased the mRNA expression levels of anti-apoptotic NF-κBp65 and Bcl-2 0.17 (8.9/52.6)-fold and 0.22 (9.5/42.3)‑fold, respectively. The pro-apoptotic caspase-3 mRNA expression levels were upregulated 4.78 (38.7/8.1)-fold. The anti-apoptotic pAkt1, pIκBα, NF-κBp65 and Bcl-2 protein levels were downregulated to 5.1 (blot grayscales vs. control at 32.3), 3.2 (vs. 24.2), 8.5 (vs. 45.1) and 9.2 (vs. 40.3). The protein levels of pro-apoptotic caspase-3 were upregulated to 20.7 (vs. 4.7). The proliferative activity of T24 cells treated with 12.5, 25.0 and 50.0 µmol/l ursolic acid was significantly reduced compared with that of control cells (83.8, 56.2 and 31.5 vs. 97.6%, respectively, P<0.05 for each). In conclusion, ursolic acid is important in inducing apoptosis via the suppression of Akt/NF-κB signaling in T24 human bladder cancer cells and this occurs in a dose-dependent manner. Ursolic acid may therefore serve as a naturally occurring candidate drug for the prevention and treatment of bladder cancer.

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