01% to 0.5%. Acetic acid at 0.5% for 1 min induced the cell death by 80%. RGK-1 cells were more sensitive to acetic acid than RGM-l cells. Selleckchem Metabolism inhibitor KATO III cells

were more sensitive to acetic acid than RGK-1 cells. Acetic acid at 0.5% for 10 min induced almost complete cell death of ACC-MESO1 and MSTO-211H. Acetic acid is a powerful anticancer agent. Topical application of acetic acid may be a feasible approach for the treatments of gastric cancer and possibly other malignancies. Topical application of acetic acid by gastric submucosal or serosal injection can induce chronic ulcers within 3–5 days in animals, including mice, rats, cats, dogs, and mini-pigs.[1-5] These ulcer models have been used to study the ulcer healing process and the effects of anti-ulcer drugs, including H2

receptor antagonists and proton pump inhibitors, for 45 years.[3] Recently, we have established a mouse model of gastric tumor damage-and-regeneration through topical application of acetic acid in the INS-GAS mice, a genetic mouse model of spontaneous cancer.[6] In the animal study, we showed that topical application of acetic acid promptly caused the necrosis of tumor, and suggested that this simple and reliable method may be used as a cytoreductive treatment of gastric cancer in patients through endoscopy or laparoscopy.[7] Wnt signaling pathway is known to click here be a major regulator of gastrointestinal stem cells, tumorigenesis, and tumor regeneration. Using this model, we have Selumetinib nmr found that the tumor regeneration was delayed by denervation, probably via the M3 receptor-Wnt signaling-stem cell pathway.[8] In the present study, we wanted to test our hypothesis that acetic acid at very low concentration can induce directly cancer cell death. To this end, we performed an in vitro study using human and rat gastric cancer cell, as well as normal mucosal cell lines and mesothelioma cell lines. Rat gastric epithelial

cell line (RGM-1, Riken Kagaku, Kyoto, Japan), rat gastric carcinoma cell line (RGK-1), human gastric cancer cell line (KATO III, Riken Kagaku), and human mesothelioma cell lines (ACC-MESO1: RIKEN BioResource Center, Tsukuba, Japan, and MSTO-211H: ATCC, Manassas, VA, USA) were used.[9-12] Both RGM-1 and RGK-1 cells were maintained in DMEM/F-12 (Wako, Osaka, Japan) medium, whereas KATO III cells and mesothelioma cells were maintained in RPMI 1640 medium (Wako). All media were supplemented with heat-inactivated 10% fetal bovine serum (Biowest, Nuaille, France), and 100 U/mL of penicillin and 100 U/mL of streptomycin at 37°C under 5% CO2 in air. Acetic acid, HCl, or ethanol was diluted by culture medium and added to the wells. Each well was washed three times with culture medium after treatment. The pH of medium was determined by a glass electrode.