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.
Written by:
Gai L, Cai N, Wang L, Xu X, Kong X. Are you the author?
Department of Urologic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 13003, P.R. China.
Reference: Mol Med Rep. 2013 May;7(5):1673-7.
doi: 10.3892/mmr.2013.1364
PubMed Abstract
PMID: 23483134
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