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.

Blockage of epithelial to mesenchymal transition and upregulation of let 7b are critically involved in ursolic acid induced apoptosis in malignant mesothelioma cell

“…In our work Western blotting revealed that ursolic acid cleaved PARP and caspase 3 and attenuated the expression of procaspase 9, cyclin D1, pAKT, pGSK3α/β, β-catenin and NFkB in three mesothelioma cells, demonstrating that apoptosis induced by ursolic acid was mediated via caspase activation and survival gene inhibition. Similarly, previous studies showed that ursolic acid induced apoptosis via inhibition of the Wnt5/β-catenin pathway in prostate cancer cells 17 and also inhibited the cell growth via AMPK 33, ER stress 34 or Akt/NF-kB 35 in human bladder cancer cells carcinoma cells.…”

Ursolic acid protects against ulcerative colitis via anti-inflammatory and antioxidant effects in mice

“…In terms of the gastrointestinal system, UA has a direct inhibitory effect on NF-κB activation in intestinal epithelial cells stimulated by TNF-α, and in peritoneal macrophages stimulated by LPS (4). UA also suppresses NF-κB signaling in colon cancer cells (7), and other types of cancer cell (40,41). In the present study, the nuclear level of NF-κB p65 in the colon tissues of the DSS group was significantly increased, compared with that of the control group.…”

A map describing the association between effective components of traditional Chinese medicine and signaling pathways in cancer cells in vitro and in vivo

“…Ursolic acid was proved to suppress the proliferation of colon cancer cell line HEK293 by promoting degradation of β-catenin (33). In Enrlich ascites carcinoma cell line, ursolic acid acts as an inducer of apoptosis through the mitochondrial signaling pathway in intro and in vivo (34), and in T24 human bladder cancer cells, it induces apoptosis via the Akt/ NF-κB pathway (35). Ursolic acid also can induce cell death and modulate autophagy by the JNK pathway in the apoptosis-resistant human colon carcinoma cell line HCT15 and CO115 (36).…”