Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Mechanism of hesperidin-induced apoptosis in human gastric cancer AGS cells

Wangmei Yu¹, Xiaolong Xie¹, Zheke Yu² , Qingzheng Jin¹, Huizhong Wu¹

¹Department of Pharmacy, Zhejiang Quhua Hospital, 62 Wenchang Rd, Quzhou 324004; ²Department of General Surgery, Taizhou Hospital of Zhejiang Province, 150 Ximen Rd, Taizhou 317000, Zhejiang Province, PR China.

For correspondence:- Zheke Yu Email: zuo1ka@163.com

Accepted: 23 October 2019 Published: 30 November 2019

Citation: Yu W, Xie X, Yu Z, Jin Q, Wu H. Mechanism of hesperidin-induced apoptosis in human gastric cancer AGS cells. Trop J Pharm Res 2019; 18(11):2363-2369 doi: 10.4314/tjpr.v18i11.19

© 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 investigate the effect of hesperidin on apoptosis of gastric cancer (GC) AGS cells, and the underlying mechanism of action.

Methods: The inhibitory effect of hesperidin was determined in AGS cells by MTT assay. Annexin V-FITC/PI double staining and flow cytometry (FC) were used to evaluate the apoptotic activity of hesperidin, reactive oxygen species (ROS), and changes in cell apoptosis after treatment of NAC cells with NAC. expressions of B cell lymphoma/leukemia-2 (Bcl-2) and mitogen-activated protein kinase (MAPK) signaling pathway were determined by Western blotting.

Results: MTT assay data showed that hesperidin inhibited AGS and MKN-28 cells. Treatment of AGS cells with hesperidin resulted in apoptosis which manifested as nuclear condensation and cell shrinkage. Staining and FC demonstrated that hesperidin induced mitochondrial apoptosis in AGS cells and increased intracellular ROS. Pre-treatment of AGS cells with NAC inhibited hesperidin-induced apoptosis. Results from western blotting showed that the increased expressions of p-JNK, p-p38, Bad, Caspase-3 and PARP, and downregulation of anti-apoptotic proteins p-ERK and Bcl-2, indicating that hesperidin activated MAPK signaling pathway and mitochondria-dependent apoptosis in AGS cells.

Conclusion: Hesperidin promotes apoptosis in human GC AGS cells. This finding provides an insight into the development of new anti-GC drugs.

Keywords: Hesperidin, Human gastric cancer cells, Cell Apoptosis, MAPK signal pathway