title: Irsogladine maleate, a gastric mucosal protectant, suppresses intestinal polyp development in Apc-mutant mice.
abstract: This study aimed to identify gastric mucosal protectants that suppress intestinal tumorigenesis in a mouse model. We chose six gastric mucosal protectants (ecabet sodium hydrate, irsogladine maleate, rebamipide, sofalcone, teprenone and troxipide) and examined their effects on the activity of oxidative stress-related transcriptional factors, including AP-1, NF-jB, NRF2, p53 and STAT3, in Caco-2 cells using a luciferase reporter gene assay. Among the six protectants, irsogladine maleate clearly inhibited NF-jB and AP-1 transcriptional activity. Furthermore, the chemopreventive property of irsogladine maleate was examined in a Min mouse model of familial adenomatous polyposis. Treatment with irsogladine maleate at doses of 5 and 50 ppm significantly reduced the number of intestinal polyps to 69% and 66% of the untreated control value, respectively. In these polyps, mRNA levels of the downstream targets of NF-jB, such as IL-1β and IL-6, were decreased by irsogladine maleate treatment. Moreover, the levels of oxidative stress-related markers, reactive carbonyl species, in the livers of Min mice were clearly decreased following the administration of irsogladine maleate. This study demonstrated that irsogladine maleate suppresses intestinal polyp formation in Min mice partly through the NF-jB signaling pathway, thus reducing oxidative stress.
authors: Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.|Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
authors: Wakana
authors: W
authors: Onuma
authors: Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
authors: Susumu
authors: S
authors: Tomono
authors: Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
authors: Shinngo
authors: S
authors: Miyamoto
authors: Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tokyo, Japan.
authors: Gen
authors: G
authors: Fujii
authors: Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
authors: Takahiro
authors: T
authors: Hamoya
authors: Division of Molecular Biology, Nagasaki International University, Nagasaki, Japan.
authors: Kyoko
authors: K
authors: Fujimoto
authors: Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
authors: Noriyuki
authors: N
authors: Miyoshi
authors: Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
authors: Fumio
authors: F
authors: Fukai
authors: Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
authors: Keiji
authors: K
authors: Wakabayashi
authors: Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.|Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tokyo, Japan.
authors: Michihiro
authors: M
authors: Mutoh
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017491:Genes, APC / Q000502:physiology*; D006801:Humans; D007124:Immunoenzyme Techniques; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007417:Intestinal Polyps / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014227:Triazines / Q000494:pharmacology*
chemical_list: D000897:Anti-Ulcer Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D014227:Triazines; C041836:irsogladine
keywords: Apc-mutant mice; NF-kB; cancer chemoprevention; irsogladine maleate; reactive carbonyl species