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

• Published in: Redox report : communications in free radical research Vol. 29; no. 1; p. 2313366
• Main Authors: Liu, Jian, Li, Shu-Mei, Tang, Yan-Jun, Cao, Jing-Long, Hou, Wen-Shuang, Wang, An-Qi, Wang, Chang, Jin, Cheng-Hao
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Group 01.12.2024
• Subjects: Apoptosis; cell apoptosis; cell cycle; Cell Line, Tumor; cell migration; Cell Proliferation; Flavonoids - pharmacology; gastric cancer; Glycogen Synthase Kinase 3 beta - metabolism; Glycogen Synthase Kinase 3 beta - pharmacology; Humans; Jaceosidin; Proto-Oncogene Proteins c-akt - metabolism; reactive oxygen species; Reactive Oxygen Species - metabolism; Signal Transduction; Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; gastric cancer; cell cycle; network pharmacology; reactive oxygen species; cell apoptosis; cell migration; cytotoxicity; Jaceosidin
• ISSN: 1351-0002; 1743-2928; 1743-2928
• DOI: 10.1080/13510002.2024.2313366

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.