Helicobacter pylori infection modulates endogenous hydrogen sulfide production in gastric cancer AGS cells.

BACKGROUND: Persistent Helicobacter pylori infection induces gastric mucosal atrophy, which is a precancerous condition. Hydrogen sulfide (H2 S), a gaseous biological transmitter, has been implicated in both the physiological functions of the gastrointestinal tract and its diseases. To understand gastric epithelial cell response against H pylori infection, we investigated the metabolic changes of gastric cancer cells co-cultured with H pylori and observed the modulation of endogenous H2 S production. MATERIALS AND METHODS: Gastric cancer AGS cells were co-cultured with an H pylori standard strain possessing bacterial virulence factor CagA (ATCC 43504) and a strain without CagA (ATCC 51932). Three hours after inoculation, the cells were subjected to metabolomics analysis using gas chromatography-tandem mass spectrometry (GC-MS/MS). Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and pathway analysis were performed. In addition, intracellular H2 S levels were measured by using HSip-1 fluorescent probe. RESULTS: Results of OPLS-DA showed a significant difference between the metabolism of untreated control cells and cells inoculated with the H pylori strains ATCC 51932 or ATCC 43504, mainly due to 45 metabolites. Pathway analysis with the selected metabolites indicated that methionine metabolism, which is related to H2 S production, was the most frequently altered pathway. H pylori-inoculated cells produced more endogenous H2 S than control cells. Moreover, ATCC 43504-inoculated cells produced less H2 S than ATCC 51932-inoculated cells. CONCLUSIONS: H pylori infection modulates endogenous H2 S production in AGS cells, suggesting that H2 S might be one of the bioactive molecules involved in the biological mechanisms of gastric mucosal disease including mucosal atrophy.

Cardenolide glycosides from the seeds of Digitalis purpurea exhibit carcinoma-specific cytotoxicity toward renal adenocarcinoma and hepatocellular carcinoma cells.

Four cardenolide glycosides, glucodigifucoside (2), 3'-O-acetylglucoevatromonoside (9), digitoxigenin 3-O-ß-D-glucopyranosyl-(1 → 4)-ß-D-glucopyranosyl-(1 → 4)-3-O-acetyl-ß-D-digitoxopyranoside (11), and purpureaglycoside A (12), isolated from the seeds of Digitalis purpurea, exhibited potent cytotoxicity against human renal adenocarcinoma cell line ACHN. These compounds exhibited significantly lower IC50 values against ACHN than that against normal human renal proximal tubule-derived cell line HK-2. In particular, 2 exhibited the most potent and carcinoma-specific cytotoxicity, with a sixfold lower IC50 value against ACHN than that against HK-2. Measurement of cyclin-dependent kinase inhibitor levels revealed that upregulation of p21/Cip1 expression was involved in the carcinoma-specific cytotoxicity of 2. Further, compound 2 also exhibited the carcinoma-specific cytotoxicity toward hepatocellular carcinoma cell line.