Berberine hydrochloride inhibits bladder cancer cells and induces apoptosis by inhibiting the PI3k/Akt signal route

Purpose: To study the effect of berberine hydrochloride on G2/M phase of the cell cycle, and the associated mechanism of action.Methods: Human bladder cancer cell line UMUC3 was cultured with graded concentrations of berberine hydrochloride (50, 100, and 200 & mu;M) for 24 h. Cell cycle distribution and apoptosis of UMUC3 cells were analyzed by flow cytometry. Levels of PI3K/Akt signal route-associated proteins in UMUC3 cells were determined using immunoblotting.Results: There were higher numbers of G2/M phase cells in each berberine hydrochloride dose group than in the control cells, and it increased with increase in berberine dose. The population of G0/G1 phase cells in each berberine dose group was significantly and dose-reliantly lower than control value. Increase in berberine dose resulted in increase in p21 protein expression, while protein expressions of CDK1, cycling B1, and CDC25C were reduced (p < 0.05). Apoptosis level was significantly higher in each dose group and was accentuated with increase in berberine dose (p < 0.05). Immunoblot results showed that with increase in dose, there was up-regulation in protein expressions of Bax, and c-caspases-9/3, while the protein expressions of bcl-2, caspases-3/9, and PARP were reduced. Western blot assay data showed that expressions of PI3K p85 and p-Akt proteins decreased, while protein expression level of PTEN increased with increase in berberine dose. In contrast, Akt protein levels were comparable in all groups.Conclusion: Berberine hydrochloride induces arrest of bladder cancer cells at G2/M phase and accelerates their apoptosis via a mechanism related to inhibition of PI3k/Akt pathway. Thus, berberine hydrochloride has potentials for use as a drug for the management of bladder cancer.