Hydrogen Sulfide Inhibits -Induced Gastric Fibroblast Activation: Implications for Cancer Prevention.

Early prevention of pathological changes underlying gastric cancer (GC) development is a critical strategy, offering the most effective opportunity to limit malignant progression and improve patient outcomes. We have previously demonstrated that () () contributes to GC development by activating gastric fibroblasts toward CAF-like phenotype, eliciting aggressive, cancer stem cells (CSCs)-related malignant transformation of LGR5 normal epithelial cells. A key mediator of these processes appears to be the NF-κB/STAT3 axis. Therefore, our aim was to investigate the protective role of hydrogen sulfide (HS) as a potential novel strategy for counteracting -induced fibroblast reprogramming. Human fibroblasts were infected with () for 120 h. The fast-releasing HS donor NaHS (50, 100, 200 and 400 µM) was added every 24 h. Activation markers, corresponding signaling pathways, HS release and activities of HS-metabolizing enzymes were determined. NaHS reduced -induced fibroblast activation and their pro-inflammatory, pro-tumorigenic markers, which was associated with the inhibition of NF-κB/STAT3 axis and Twist expression. Additionally, it modulated sulfur metabolism while preserving sulfur-enzyme homeostasis. NaHS limited adhesion (high doses), reduced reinfection-induced activation and increased sensitivity of to metronidazole. These findings suggest that HS signaling may represent a modulatory factor of NF-κB/STAT3-driven inflammatory responses during infection and warrant further investigation.