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


Wangmei Yu
Xiaolong Xie
Zheke Yu
Qingzheng Jin
Huizhong Wu

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 VFITC/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.


Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996