Effect of acacetin on inhibition of apoptosis in Helicobacter pylori-infected gastric epithelial cell line

Abstract

BACKGROUND

Helicobacter pylori (H. pylori) infection can cause extensive apoptosis of gastric epithelial cells, serving as a critical catalyst in the progression from chronic gastritis, gastrointestinal metaplasia, and atypical gastric hyperplasia to gastric carcinoma. Prompt eradication of H. pylori is paramount for ameliorating the pathophysiological conditions associated with chronic inflammation of the gastric mucosa and the primary prevention of gastric cancer. Acacetin, which has multifaceted pharmacological activities such as anti-cancer, anti-inflammatory, and antioxidative properties, has been extensively investigated across various domains. Nevertheless, the impact and underlying mechanisms of action of acacetin on H. pylori-infected gastric mucosal epithelial cells remain unclear.

AIM

To explore the defensive effects of acacetin on apoptosis in H. pylori-infected GES-1 cells and to investigate the underlying mechanisms.

METHODS

GES-1 cells were treated with H. pylori and acacetin in vitro. Cell viability was assessed using the CCK-8 assay, cell mortality rate via lactate dehydrogenase assay, alterations in cell migration and healing capacities through the wound healing assay, rates of apoptosis via flow cytometry and TUNEL staining, and expression levels of apoptosis-associated proteins through western blot analysis.

RESULTS

H. pylori infection led to decreased GES-1 cell viability, increased cell mortality, suppressed cell migration, increased rate of apoptosis, increased expressions of Bax and cle-caspase3, and decreased Bcl-2 expression. Conversely, acacetin treatment enhanced cell viability, mitigated apoptosis induced by H. pylori infection, and modulated the expression of apoptosis-regulatory proteins by upregulating Bcl-2 and downregulating Bax and cleaved caspase-3.

CONCLUSION

Acacetin significantly improved GES-1 cell viability and inhibited apoptosis in H. pylori-infected GES-1 cells, thereby exerting a protective effect on gastric mucosal epithelial cells.

Keywords: Gastric epithelial GES-1 cells; Helicobacter pylori; Infection; Acacetin; Antibiotic resistance; Apoptosis

Core Tip: Helicobacter pylori (H. pylori), a common human microaerophilic gram-negative rod, is crucial in the progression of chronic gastritis, gastrointestinal metaplasia, and gastric atypical hyperplasia to gastric cancer. We have examined the protective role of acacetin against apoptosis in H. pylori-infected GES-1 cells. However, the role of acacetin in the apoptosis of gastric epithelial cells induced by H. pylori infection has not been previously reported. Therefore, this study offers a new perspective for early intervention in H. pylori-induced chronic gastritis and may provide synergistic effects and novel therapeutic directions for the clinical eradication of H. pylori in conjunction with the standard quadruple therapy.