Jaceosidin induces apoptosis and inhibits migration in AGS gastric cancer cells by regulating ROS-mediated signaling pathways

ABSTRACT

Jaceosidin (JAC) is a natural flavonoid with anti-oxidant and other pharmacological activities; however, its anti-cancer mechanism remains unclear. We investigated the mechanism of action of JAC in gastric cancer cells. Cytotoxicity and apoptosis assays showed that JAC effectively killed multiple gastric cancer cells and induced apoptosis in human gastric adenocarcinoma AGS cells via the mitochondrial pathway. Network pharmacological analysis suggested that its activity was linked to reactive oxygen species (ROS), AKT, and MAPK signaling pathways. Furthermore, JAC accumulated ROS to up-regulate p-JNK, p-p38, and IκB-α protein expressions and down-regulate the p-ERK, p-STAT3, and NF-κB protein expressions. Cell cycle assay results showed that JAC accumulated ROS to up-regulate p21 and p27 protein expressions and down-regulate p-AKT, CDK2, CDK4, CDK6, Cyclin D1, and Cyclin E protein expressions to induce G0/G1 phase arrest. Cell migration assay results showed JAC accumulated ROS to down-regulate Wnt-3a, p-GSK-3β, N-cadherin, and β-catenin protein expressions and up-regulate E-cadherin protein expression to inhibit migration. Furthermore, N-acetyl cysteine pre-treatment prevented the change of these protein expressions. In summary, JAC induced apoptosis and G0/G1 phase arrest and inhibited migration through ROS-mediated signaling pathways in AGS cells.

KEYWORDS:

• Jaceosidin
• gastric cancer
• reactive oxygen species
• cell apoptosis
• cell cycle
• cell migration
• cytotoxicity
• network pharmacology

Acknowledgments

We thank Taylor & Francis Editing Services (www.tandfeditingservices.com) for providing language assistance.

Declaration of interest statement

The authors declare that they have no competing financial interests in this paper.

Data availability statement

The data used to support the findings of this study are available from the corresponding authors upon request.

Additional information

Funding

This research was supported by [Funding Agency #1] Central Government Supports Local College Reform and Development Fund Talent Training Project [grand number: 2020GSP16]; [Funding Agency #2] Heilongjiang Province Key Research and Development Plan Guidance Project [grand number: GZ20220039]; [Funding Agency #3] Heilongjiang Touyan Innovation Team Program (grand number: 2019HTY078]; [Funding Agency #4] Postgraduate Innovative Research Project of Heilongjiang Bayi Agricultural University [grand number: YJSCX2022-Y55], and [Funding Agency #5] Postgraduate Innovative Research Project of Heilongjiang Bayi Agricultural University [grand number: YJSCX2023-Y62].