Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Wogonoside exerts potential anti-tumor activity against bladder cancer in vivo and in vitro via regulation of GSK-3β/ERK/AKT signaling pathway

Jiexiang Chen¹, Yong Cao², Li Tang⁴, Yan Li², Xiaolan Yu³, Jiyi Xia⁴

¹Department of Urinary Surgery; ²Experimental Medicine Center, The Affiliated Hospital of Southwest Medical University, Luzhou 646000; ³Department of Obstetrics and Gynecology, The Affiliated Hospital of Traditional Chinese Medicine of Southwest Medical University, Luzhou 646000; ⁴School of Medical Information and Engineering, Southwest Medical University, Luzhou 646000, PR China.

For correspondence:- Jiyi Xia Email: xiajiyi6600@163.com Tel:+868303160048

Accepted: 20 June 2019 Published: 28 July 2019

Citation: Chen J, Cao Y, Tang L, Li Y, Yu X, Xia J. Wogonoside exerts potential anti-tumor activity against bladder cancer in vivo and in vitro via regulation of GSK-3β/ERK/AKT signaling pathway. Trop J Pharm Res 2019; 18(7):1385-1390 doi: 10.4314/tjpr.v18i7.3

© 2019 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To explore the antitumor activity of wogonoside on bladder cancer, and its underlying mechanism of action.

Methods: Methyl thiazolyl tetrazolium (MTT) assay was applied to determine the anti-proliferative activity of wogonoside (2 - 128 μM) on bladder cancer 5637 cell line at various times, and the half-maximal inhibitory concentration (IC₅₀) was measured. The antitumor activity of wogonoside (30 mg/kg, ip) against bladder cancer 5637 cell line was evaluated in nude mice bearing human bladder cancer 5637 cells. Additionally, western blotting and enzyme-linked immunosorbent assay (ELISA) were carried out to investigate the levels of the caspase-3, caspase-9, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X-protein (Bax), phosphorylated (p)-glycogen synthase kinase (GSK)-3β, p-extracellular signal-regulated kinases (p-ERK), and p-(protein kinase B) AKT.

Results: The in vitro results revealed that wogonoside exerted anti-proliferative activity against bladder cancer 5637 cells with an IC₅₀ of 20.59 μM (p < 0.01), in a concentration- and time-dependent manner. Furthermore, wogonoside treatment also significantly suppressed tumor volume in mice (p < 0.01). The potential mechanisms were mainly associated with apoptosis mediated by mitochondria via up-regulation of caspase-3, caspase-9, and Bax levels and down-regulation of Bcl-2, p-GSK-3β, p-ERK, and p-AKT.

Conclusion: The results reveal that wogonoside has remarkable anti-tumor potentials against bladder cancer. Further translational studies are warranted to test the clinical application of this medicinal agent in bladder cancer.

Keywords: Bladder cancer, Wogonoside, GSK-3β/ERK/AKT signaling pathway, Apoptosis, Cell line 5637