Affiliation:
1. Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University
2. Hemodialysis Center, Daqing Oilfield General Hospital
3. Department of Food Science and Engineering, College of Food Science, Heilongjiang Bayi Agricultural University
4. Hospital Clinical Laboratory, Heilongjiang Bayi Agricultural University
Abstract
Abstract
Chrysosplenetin B (CHR) is a flavonoid compound with various pharmacological activities. This study aimed to investigate the effect and mechanism of CHR on gastric cancer (GC). A cell counting Kit 8 assay results showed that CHR had a good cytotoxic effect in twelve types of GC cell lines. Annexin-V/PI staining, flow cytometry, and western blot analysis results showed that CHR induced mitochondrial-dependent apoptosis of AGS cells by decreasing mitochondrial membrane potential and increasing the expression levels of Bad/Bcl-2 homologous dimer proteins. Network pharmacological analysis results showed that there were twenty high-value signaling pathways correlated with CHR and GC, among which AKT, MAPK, and STAT3 signaling pathways were closely related to the CHR induced apoptosis signaling pathways on AGS cells. Further through western blot analysis results showed that the protein expression levels of p-AKT, p-ERK, and p-STAT3 were significantly decreased, while the protein expression levels of p-JNK and p-p38 were significantly increased. Moreover, reactive oxygen species (ROS) analysis results showed that CHR induced ROS accumulation on AGS cells as an initial signal to regulate downstream signaling pathways. Cell cycle results showed that CHR arrested the AGS cell cycle in the G2/M phase by regulating the ROS/AKT signaling pathway. Transwell and wound healing assay results showed that CHR inhibited the invasion and migration of AGS cells by regulating ROS/Wnt-3a/GSK-3β/β-catenin signaling pathway. In conclusion, CHR inhibited cell proliferation, induced cell apoptosis, arrested the cell cycle in the G2/M phase, and inhibited invasion and migration on AGS cells.
Publisher
Research Square Platform LLC
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