Neochlorogenic acid inhibits gastric cancer cell growth through apoptosis and cell cycle arrest.

BACKGROUND: Gastric cancer is a leading cause of cancer-related deaths worldwide. It remains a significant clinical challenge due to its frequent diagnosis at advanced stages and the development of resistance to conventional therapies. Neochlorogenic acid (NCA) is a phenolic compound with reported anti-inflammatory, antioxidant, and anti-tumor properties. This study aims to elucidate the mechanisms underlying NCA's anti-tumor effects in gastric cancer. METHODS: In vitro, HGC-27 and NUGC-3 cells were treated with NCA. The half maximal inhibitory concentration (IC50) values of the two cells at 48 hours after drug treatment were 229.9 and 130.0 µM, respectively, and cell proliferation, migration, cell cycle, and apoptosis were evaluated. Western blot analysis was used to assess the expression of apoptosis-related proteins. RNA sequencing was performed to identify differentially expressed genes and affected pathways. In vivo, a xenograft model was used to assess the effect of NCA on tumor growth. RESULTS: NCA inhibited the proliferation and migration of gastric cancer cells in vitro. Cell cycle analysis showed that NCA induced G1 phase arrest. Apoptosis assays and Western blot analysis revealed that NCA promoted apoptosis. In NUGC-3 cells, NCA treatment upregulated BAX (BCL2-associated X protein, 2.2-fold), CASP3 (caspase-3, 1.5-fold), BID (BH3 interacting domain death agonist, 1.3-fold), and CYCS (cytochrome c, somatic, 1.5-fold), while downregulating BCL2 (B-cell lymphoma 2, 0.8-fold). In HGC-27 cells, more pronounced effects were observed, with BAX dramatically upregulated (9.9-fold), along with increases in CASP3 (1.7-fold), BID (2.4-fold), and CYCS (1.4-fold), and a significant downregulation of BCL2 (to 0.2-fold). RNA sequencing identified significant changes in gene expression related to cancer pathways. In vivo, NCA significantly suppressed tumor growth. CONCLUSIONS: NCA demonstrates significant anti-tumor activity against gastric cancer cells both in vitro and In vivo, suggesting its potential as a therapeutic agent. These findings suggest that NCA suppresses gastric cancer via apoptosis and cell cycle arrest and warrants further preclinical and clinical evaluation as a potential therapeutic strategy for gastric cancer.