Oleanolic acid suppresses the proliferation of human bladder cancer by Akt/mTOR/S6K and ERK1/2 signaling

Abstract

Oleanolic acid has significant pharmacological activities, such as anti-tumor, regulating blood sugar level and liver protection, which are more effective compared with free aglyconeoleanolic acid. However, it is still unknown if oleanolic acid affects the proliferation of human bladder cancer. We utilized T24 cells to study the effect of oleanolic acid on the proliferation and apoptosis of human bladder cancer. In this study, we found that the anti-cancer effect of oleanolic acid significantly suppressed cell proliferation and increased apoptosis and caspase-3 activity of T24 cells. Furthermore, Akt, mTOR and S6K protein expression was greatly inhibited in T24 cells under oleanolic acid treatment. Meanwhile, ERK1/2 of phosphorylation protein expression was significantly promoted by oleanolic acid treatment. Taken together, we provided evidences that oleanolic acid was Akt/mTOR/S6K and ERK1/2 signaling-targeting anti-tumor agent. These findings represent new evidences that oleanolic acid suppresses the proliferation of human bladder cancer by Akt/mTOR/S6K and ERK1/2 signaling, and oleanolic acid may be used to prevent human bladder cancer.

Keywords: Akt; ERK1/2; Oleanolic acid; S6K; bladder cancer; mTOR.

Figure 1

The chemical structure of oleanolic acid.

Figure 2

Oleanolic acid suppresses the cell proliferation of human bladder cancer. **P<0.01 compared with 0 μM oleanolic acid group.

Figure 3

Oleanolic acid suppresses the apoptosis of human bladder cancer. **P<0.01 compared with 0 μM oleanolic acid group.

Figure 4

Oleanolic acid suppresses the capase-3 of human bladder cancer. **P<0.01 compared with 0 μM oleanolic acid group.

Figure 5

Oleanolic acid suppresses the proliferation of human bladder cancer through Akt signaling. Akt and p-Akt protein expression using Western blot analysis (A) and statistical analysis of Akt and p-Akt protein (B) in T24 cells. **P<0.01 compared with 0 μM oleanolic acid group.

Figure 6

Oleanolic acid suppresses the proliferation of human bladder cancer through mTOR signaling. mTOR protein expression using Western blot analysis (A) and statistical analysis of mTOR protein (B) in T24 cells. **P<0.01 compared with 0 μM oleanolic acid group.

Figure 7

Oleanolic acid suppresses the proliferation of human bladder cancer through S6K signaling. S6K protein expression using Western blot analysis (A) and statistical analysis of S6K protein (B) in T24 cells. **P<0.01 compared with 0 μM oleanolic acid group.

Figure 8

Oleanolic acid suppresses the proliferation of human bladder cancer through ERK1/2 signaling. p-ERK1/2 protein expression using Western blot analysis (A) and statistical analysis of p-ERK1/2 protein (B) in T24 cells. **P<0.01 compared with 0 μM oleanolic acid group.