Irsogladine maleate, a gastric mucosal protectant, suppresses intestinal polyp development in <i>Apc</i>-mutant mice

Onuma, Wakana; Tomono, Susumu; Miyamoto, Shinngo; Fujii, Gen; Hamoya, Takahiro; Fujimoto, Kyoko; Miyoshi, Noriyuki; Fukai, Fumio; Wakabayashi, Keiji; Mutoh, Michihiro

doi:10.18632/oncotarget.7082

Cited by 16 publications

(16 citation statements)

References 29 publications

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“…Therefore, IL-6 reduction is likely involved in the polyp suppressive effects of acetazolamide. In another experiment that we previously performed, IL-6 played an important role in the development of intestinal polyps in Min mice [ 14 , 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of Acetazolamide, a Carbonic Anhydrase Inhibitor, on the Development of Intestinal Polyps in Min Mice

Noma

Fujii²,

Miyamoto³

et al. 2017

IJMS

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Colorectal cancer is a common cancer worldwide. Carbonic anhydrase (CA) catalyzes the reversible conversion of carbon dioxide to bicarbonate ion and a proton, and its inhibitor is reported to reduce cancer cell proliferation and induce apoptosis. Therefore, we asked whether acetazolamide, a CA inhibitor, could inhibit intestinal carcinogenesis. Five-week-old male Apc-mutant mice, Min mice, were fed a AIN-76A diet containing 200 or 400 ppm acetazolamide. As a result, acetazolamide treatment reduced the total number of intestinal polyps by up to 50% compared to the control group. In addition, the acetazolamide-treated group had low cell proliferation and a high apoptosis ratio in the intestinal polyp epithelial cells. Moreover, the mRNA expression level of proinflammatory cytokines, such as IL-6, involved in the cell proliferation was decreased in the polyp part of the acetazolamide-treated group. Next, we examined the effects of acetazolamide on the activation of several transcriptional factors (AP-1, HIF, HSF, NF-κB, NRF2, p53, and STAT3) using a reporter gene assay in human colon cancer cells, Caco-2 cells. Among the examined transcriptional factors, NRF2 transcriptional activation was strongly induced. NRF2-targeting genes, γGCS, GPx1, HO-1, and NQO-1, were also elevated in the intestinal polyps of acetazolamide-treated Min mice. Our results suggested that CA is involved in intestinal carcinogenesis. Acetazolamide could inhibit polyp formation through suppressing local/general cytokine levels, i.e., IL-6, via NRF2 activation.

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Section: Discussionmentioning

confidence: 99%

Impact of Acetazolamide, a Carbonic Anhydrase Inhibitor, on the Development of Intestinal Polyps in Min Mice

Noma

Fujii²,

Miyamoto³

et al. 2017

IJMS

Self Cite

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“…A π–π stacking of the 5‐ASA aromatic ring with His144 residue of Chain A could also be observed. It is worth noting that irsogladine has been shown chemopreventive properties by significantly reducing number of intestinal polyp in a mouse model [62] …”

Section: Discussionmentioning

confidence: 99%

Using Theory To Extend the Scope of Azobenzene Drugs in Chemotherapy: Novel Combinations for a Specific Delivery

Cerón‐Carrasco

Jacquemin

2021

ChemMedChem

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Gut microorganisms metabolize azobenzene compounds (Ph1−N=N−Ph2) into free aniline products (Ph1−NH2+H2N−Ph2), a process that has been largely investigated to reduce dyes residues in the textile industry. However, the action of bacterial core enzymes such as azoreductases (AzoR) might also help to deliver prodrugs that become active when they reach the colonic region, a mechanism with potential applications for the treatment of inflammatory bowel disease (IBD) and colorectal cancer. So far, three azo‐bonded prodrugs of 5‐aminosalicylic acid (5‐ASA), for example, sulfasalazine, olsalazine and balsalazide, have been used for colon‐targeted delivery. The present contribution describes the first rational design of a novel azobenzene prodrug thanks to a computational approach, with a focus on linking 5‐ASA to another approved anti‐inflammatory drug. The resulting prodrugs were assessed for their degradation upon AzoR action. Replacing the original carriers by irsogladine is found to improve action.

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“…Recently, the use of endoscopy, a minimally invasive treatment technique that aids the diagnosis and treatment of gastrointestinal (GI) disorders, has rapidly expanded in the therapeutic eld. According to this growth of endoscopy application to meet the rising clinical demand, endoscopically injectable hydrogels have attracted attention for use in endoscopic submucosal dissection (ESD), hemostasis, mucus protection, and wound healing, among others (Onuma et al, 2016). ese hydrogels may be pre-formed or precursor liquid-type hydrogels, which form hydrogels at the applied site.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Endoscopic Injectability and Post-Ejection Dripping of Yield Stress Fluids: Laponite, Carbopol and Xanthan Gum

Madhavikutty

Ohta

Pan

et al. 2021

J. Chem. Eng. Japan

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Yield stress uids, which show reversible gel-sol transition and a decrease in viscosity via shear, are expected for endoscopic applications. However, quantitative analyses of such uids, including pressure drop during endoscopic catheter delivery and post-delivery dripping, have not yet been conducted from a chemical engineering perspective. In this study, we fabricated an equipment setup comprising an endoscopic catheter and a model gastrointestinal (GI) duct to which di erent concentrations of three model yield stress uids, speci cally, laponite (LAP), Carbopol (CP), and xanthan gum (XG), were applied and compared. We clari ed the tradeo between the pressure drop through the catheter and dripping on the GI duct model. In terms of operability, LAP performed better than CP and XG. The e ect of gravity on dripping, which is greatly a ected by the position of a patient, was discussed. Finally, the relationship between the operability and rheological properties such as viscosity, yield stress, and restructuring time of the three materials were quantitatively studied.

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

Cited by 16 publications

References 29 publications

Impact of Acetazolamide, a Carbonic Anhydrase Inhibitor, on the Development of Intestinal Polyps in Min Mice

Impact of Acetazolamide, a Carbonic Anhydrase Inhibitor, on the Development of Intestinal Polyps in Min Mice

Using Theory To Extend the Scope of Azobenzene Drugs in Chemotherapy: Novel Combinations for a Specific Delivery

Analysis of Endoscopic Injectability and Post-Ejection Dripping of Yield Stress Fluids: Laponite, Carbopol and Xanthan Gum

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