Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Xiuling Jiang¹, Yougen Hu², Jianming Peng¹, Landi Su¹, Tingyong Wu³

¹Medical College, Yangzhou Polytechnic College, Yangzhou 225009, China; ²Department of Surgery â…¢, Jiangsu Armed Police Corps Hospital, Yangzhou 225003, China; ³Urological surgery, Yangzhou Oriental Hospital, Yangzhou 225009, Jiangsu Province, China.

For correspondence:- Tingyong Wu Email: wutingyong1978@163.com

Accepted: 28 May 2023 Published: 30 June 2023

Citation: Jiang X, Hu Y, Peng J, Su L, Wu T. Berberine hydrochloride inhibits bladder cancer cells and induces apoptosis by inhibiting the PI3k/Akt signal route. Trop J Pharm Res 2023; 22(6):1161-1166 doi: 10.4314/tjpr.v22i6.3

© 2023 The authors.
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Abstract

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 μM) 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.

Keywords: Berberine hydrochloride, PI3kakt pathway, Bladder cancer cells, G2M phase arrest, Apoptosis