Isovanillin, a natural coumarin compound, exhibits biological functions; however, its anti-gastric cancer process is not well understood. This research examined the pathway underlying isovanillin’s effects on gastric cancer cells. Cell viability assays demonstrated that isovanillin effectively reduced the viability of various gastric cancer cell lines. Network pharmacological analysis identified 41 key targets implicated in isovanillin’s anti-gastric cancer activity, highlighting the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), mitogen-activated protein kinase (MAPK), and reactive oxygen species (ROS) pathways as critical components. Apoptosis assays revealed that isovanillin promoted apoptosis by upregulating the manifestation of p-p38 and p-JNK and suppressing p-ERK and p-STAT3. Cellular cycle examination revealed that isovanillin triggered G2/M stage block via the suppression of p-PI3K, p-AKT, cell cycle regulators 1/2 (CDK1/2), and cyclin B1, and the increase of cell cycle inhibitor 1A (p21) and cell cycle inhibitor 1B (p27). Cell metastasis assays showed that isovanillin suppressed the migration of MKN-45 cells through diminishing the concentrations of p-PI3K, p-AKT, N-cadherin, matrix metalloproteinase-2, as well as matrix metalloproteinase-9, while increasing E-cadherin expression. Furthermore, isovanillin exerted its anti-gastric cancer effects by promoting ROS accumulation, thereby modulating associated signaling pathways. The ROS scavenger N-acetyl- l -cysteine reversed isovanillin-induced protein expression changes. In conclusion, isovanillin induces apoptosis, G2/M phase arrest, and inhibits MKN-45 cell migration by mediating ROS to regulate the MAPK and PI3K signaling pathways.
Wen et al. (Wed,) studied this question.