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Oncotarget. 2016 Feb 23;7(8):8640-52. doi: 10.18632/oncotarget.7082.

Irsogladine maleate, a gastric mucosal protectant, suppresses intestinal polyp development in Apc-mutant mice.

Author information

1
Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
2
Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
3
Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
4
Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tokyo, Japan.
5
Division of Molecular Biology, Nagasaki International University, Nagasaki, Japan.

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.

KEYWORDS:

Apc-mutant mice; NF-kB; cancer chemoprevention; irsogladine maleate; reactive carbonyl species

PMID:
26840084
PMCID:
PMC4890993
DOI:
10.18632/oncotarget.7082
[Indexed for MEDLINE]
Free PMC Article

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