Induction of apoptosis in cultured rat gastric epithelial cells by ipriflavone: comparison with indomethacin.
Based on a previous report illustrating severe gastrointestinal side effects with ipriflavone, we examined the effects of ipriflavone on cell death in cultured rat gastric epithelial cells compared with other chemicals, including indomethacin. Low concentrations of ipriflavone, indomethacin, dexamethasone, and estradiol all induced cell death in gastric epithelial cells. DNA from cultured cells treated with ipriflavone showed fragmentation by electrophoresis. Also, some of the cultured cells treated with ipriflavone were positively stained by TUNEL. In order to confirm induction of apoptosis by ipriflavone, rescue from ipriflavone-induced cell death with Z-DEVD-FMK (0.02-0.1 mM), which is a caspase 3 inhibitor, or PGE(2) (0.01-10 mM), was tested. Only Z-DEVD-FMK was observed to rescue the cells from cell death. Similar results were obtained with indomethacin, dexamethasone and estradiol. These results suggest that ipriflavone, indomethacin, dexamethasone and estradiol induce cell death of cultured rat gastric epithelial cells by apoptosis.
Tani
Satoru
S
Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan. tanisato@josai.ac.jp
Matsuda
Kazuki
K
Tanaka
Toru
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology* / Q000633:toxicity; D007529:Isoflavones / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D007529:Isoflavones; C018986:ipriflavone; D007213:Indomethacin