05). However, this additional effect of esomeprazole on the cytotoxicity of chemotherapeutics was higher in cisplatin treated cells (resulting in an overall cytotoxicity of 88-99% after combined treatment) than in 5 FU-treated cells (resulting in an overall cytotoxicity of only about 80-97% after combined treatment; p < 0.05). Figure 3 Effect of PPI treatment on otherwise untreated cells and on CTX treated cells. Presents an overview of the impact of esomeprazole treatment on otherwise untreated cells or on cells that were treated simultaneously with chemotherapeutics (3A: SCC; 3B: EAC). Tumour cells were treated with either esomeprazole alone at different
concentrations (50 μM: “sub-lethal”, 86-100% cell survival; 250 μM: “lethal”, PD173074 20-30% cell survival; 350 μM: “highly lethal”, <10% cell survival), or with cisplatin or 5-FU at the respective LD50 concentrations, or Talazoparib concentration with esomeprazole and chemotherapeutics together. The upper graphs present an overview of the relative cell survival of the respective groups (PPI treated cells versus chemotherapy (CTX) treated cells versus PPI + CTX treated cells). The lower graphs present an overview about the additional
cytotoxic effect of PPI treatment on otherwise untreated cells (PPI w/o CTX) or on CTX treated cells (PPI w CTX). PPI: proton pump inhibitor esomeprazole. CTX: chemotherapy. *: statistically significant different compared to control. Esomeprazole does not lead to intracellular acidification and {Selleck Anti-infection Compound Library|Selleck Antiinfection Compound Library|Selleck Anti-infection Compound Library|Selleck Antiinfection Compound Library|Selleckchem Anti-infection Compound Library|Selleckchem Antiinfection Compound Library|Selleckchem Anti-infection Compound Library|Selleckchem Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|buy Anti-infection Compound Library|Anti-infection Compound Library ic50|Anti-infection Compound Library price|Anti-infection Compound Library cost|Anti-infection Compound Library solubility dmso|Anti-infection Compound Library purchase|Anti-infection Compound Library manufacturer|Anti-infection Compound Library research buy|Anti-infection Compound Library order|Anti-infection Compound Library mouse|Anti-infection Compound Library chemical structure|Anti-infection Compound Library mw|Anti-infection Compound Library molecular weight|Anti-infection Compound Library datasheet|Anti-infection Compound Library supplier|Anti-infection Compound Library in vitro|Anti-infection Compound Library cell line|Anti-infection Compound Library concentration|Anti-infection Compound Library nmr|Anti-infection Compound Library in vivo|Anti-infection Compound Library clinical trial|Anti-infection Compound Library cell assay|Anti-infection Compound Library screening|Anti-infection Compound Library high throughput|buy Antiinfection Compound Library|Antiinfection Compound Library ic50|Antiinfection Compound Library price|Antiinfection Compound Library cost|Antiinfection Compound Library solubility dmso|Antiinfection Compound Library purchase|Antiinfection Compound Library manufacturer|Antiinfection Compound Library research buy|Antiinfection Compound Library order|Antiinfection Compound Library chemical structure|Antiinfection Compound Library datasheet|Antiinfection Compound Library supplier|Antiinfection Compound Library in vitro|Antiinfection Compound Library cell line|Antiinfection Compound Library concentration|Antiinfection Compound Library clinical trial|Antiinfection Compound Library cell assay|Antiinfection Compound Library screening|Antiinfection Compound Library high throughput|Anti-infection Compound high throughput screening| extracellular alkalisation in esophageal cancer cell lines The literature suggests that PPIs mediate their effects on tumour cells
via disruption of the intra-extracellular Methane monooxygenase pH-gradient and accumulation of protons in the cytosol of cancer cells. We hypothesized that the observed suppressive effect of esomeprazole on cell survival, metastatic potential and sensitivity towards cisplatin and 5-FU in both esophageal cancer subtypes might be caused by intracellular acidification/extracellular alkalisation. Therefore, we investigated the intracellular pH in both tumour subtypes, and the proton concentration in the extracellular space (culture medium). We could not detect any differences in the intracellular pH between cells that were exposed to esomeprazole (LD50) for 24/48 hours and untreated controls. However, surprisingly, the intracellular pH was significantly higher in cells (SCC and EAC) treated with esomeprazole for 72 hours compared to untreated controls (p ≤ 0.017). In addition, the concentration of protons was significantly higher in the extracellular space of esomeprazole treated cells (72 hours, LD50) compared to untreated controls (p ≤ 0.001) (see Figures 4 and 5). Figure 4 Effect of PPI treatment on intracellular pH. The figure presents the results of intracellular pH measurement after 24/48/72 hours of esomeprazole treatment (LD50) in SCC (A) and EAC (B) cells.