Chemopreventive and Differentiation-Inducing Agents Can Prevent Chemotherapy-Induced Increase of Colon Cancer Stem Cell Population

Backgrounds: Proton pump inhibitor (PPI) inhibits gastric acid secretion by suppressing H+/K+-ATPase of parietal cells and also has antioxidant and anti-inflammatory effect. Acid pump antagonist (APA), another class of PPI, is a reversible selective inhibitor of active acid pumps. Reactive oxygen species (ROS) such as superoxide, hydroxyl radical and hydrogen peroxide can cause oxidative damage and cancer development in gastric epithelial cells. In this study, we investigated whether APA (revaprazan) and PPI (omeprazole) inhibit ethanolinduced DNA damage by suppressing the expression of ROS in human gastric AGS cells. Methods: AGS cells (ATCC CRL 1739) were incubated with ethanol (from 1 to 10%) during 1hr. MTT and Comet assay were performed to determine the proper concentration of ethanol to induce cytotoxicity and DNA damage in AGS cells, respectively. We determined the appropriate concentration of ethanol to 5%. AGS cells were incubated in the proper concentrations of revaprazan or omeprazole for 24 h prior to exposure to 5% ethanol for 1 h. We analyzed the change of ethanol-induced DNA damage and ROS levels by the pretreatment with revaprazan or omeprazole. The expressions of ROS induced by ethanol were detected by a laser scanning confocal microscope. . Results: There were significant decreases of ethanol-induced DNA damage in AGS cells pretreated with revaprazan and omeprazole. Ethanol induced the increase of ROS in AGS cells. Revaprazan and omeprazole inhibited the increase of ROS induced by ethanol dose-dependently at the concentration range of decreasing DNA damage in AGS cells. Conclusions: APA (revaprazan) and PPI (omeprazole) have the capacity to decrease ethanol-induced DNA damage in human gastric epithelial cells by suppressing the expression of ROS. They might have cytoprotective effect against oxidative stress and DNA damage in gastric mucosa.