Inhibitory Effect of Astaxanthin on Gene Expression Changes in Helicobacter pylori-Infected Human Gastric Epithelial Cells

Helicobacter pylori (H. pylori) infection promotes gastric carcinogenesis by increasing oxidative stress, inflammation, and dysregulation of cell survival and proliferation of gastric epithelial cells. Astaxanthin (ASTX), a bioactive carotenoid, exhibits antioxidant and anticancer effects by modulating aberrant signaling pathways that lead to dysregulation of cell death and proliferation. To elucidate the molecular mechanism of H. pylori-induced gastric carcinogenesis and to examine the inhibitory effect of ASTX on H. pylori-induced gastric epithelial cell gene expression changes, we performed comparative RNA-sequencing (RNA-Seq) analysis for H. pylori-infected gastric epithelial cells treated with or without ASTX. RNA-Seq results reveal that differentially expressed genes (DEGs) in H. pylori-infected cells were mainly associated with the Wnt/beta-catenin signaling pathway, which is related to cell proliferation. ASTX significantly reversed H. pylori-induced transcriptional alterations of the key mediators involved in beta-catenin signaling, notably, porcupine (gene symbol, PORCN), spermine oxidase (SMOX), bone morphogenetic protein (BMP) and activin membrane-bound inhibitor (BAMBI), SMAD family member 4 (SMAD4), transforming growth factor-beta 1 (TGFB1), Fos-like 1 (FOSLI), and c-myc (MYC). We suggest that ASTX may be a potential therapeutic agent that can suppress H. pylori-induced proliferation-associated gene expression changes, in part, by counter-regulating the Wnt/beta-catenin signaling pathway.

Automated summary

Helicobacter pylori infection promotes gastric carcinogenesis by increasing oxidative stress, inflammation, and dysregulation of cell survival and proliferation of gastric epithelial cells. Astaxanthin exhibits antioxidant and anticancer effects by modulating aberrant signaling pathways that lead to dysregulation of cell death and proliferation. Astaxanthin significantly reversed H. pylori-induced transcriptional alterations of key mediators involved in the Wnt/beta-catenin signaling pathway, suggesting its potential as a therapeutic agent to counter-regulate proliferation-associated gene expression changes induced by H. pylori.