title: Ursolic acid induces apoptosis via Akt/NF-κB signaling suppression in T24 human bladder cancer cells.
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.
authors.affiliation: Department of Urologic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 13003, PR China. gailong2000@sina.com
authors.forename: Long
authors.initials: L
authors.lastname: Gai
authors.forename: Na
authors.initials: N
authors.lastname: Cai
authors.forename: Lingling
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Xu
authors.forename: Xiangbo
authors.initials: X
authors.lastname: Kong
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D014315:Triterpenes / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D000097245:Ursolic Acid
chemical_list: D016328:NF-kappa B; D009363:Neoplasm Proteins; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D014315:Triterpenes; D000097245:Ursolic Acid