{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361137044100520064.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.1010203108"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.1010203108"}}],"dc:title":[{"@value":"Polyamine catabolism contributes to enterotoxigenic<i>Bacteroides fragilis</i>-induced colon tumorigenesis"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>It is estimated that the etiology of 20–30% of epithelial cancers is directly associated with inflammation, although the direct molecular events linking inflammation and carcinogenesis are poorly defined. In the context of gastrointestinal disease, the bacterium enterotoxigenic<jats:italic>Bacteroides fragilis</jats:italic>(ETBF) is a significant source of chronic inflammation and has been implicated as a risk factor for colorectal cancer. Spermine oxidase (SMO) is a polyamine catabolic enzyme that is highly inducible by inflammatory stimuli resulting in increased reactive oxygen species (ROS) and DNA damage. We now demonstrate that purified<jats:italic>B. fragilis</jats:italic>toxin (BFT) up-regulates SMO in HT29/c1 and T84 colonic epithelial cells, resulting in SMO-dependent generation of ROS and induction of γ-H2A.x, a marker of DNA damage. Further, ETBF-induced colitis in C57BL/6 mice is associated with increased SMO expression and treatment of mice with an inhibitor of polyamine catabolism,<jats:italic>N</jats:italic><jats:sup>1</jats:sup>,<jats:italic>N</jats:italic><jats:sup>4</jats:sup>-bis(2,3-butandienyl)-1,4-butanediamine (MDL 72527), significantly reduces ETBF-induced chronic inflammation and proliferation. Most importantly, in the multiple intestinal neoplasia (Min) mouse model, treatment with MDL 72527 reduces ETBF-induced colon tumorigenesis by 69% (<jats:italic>P</jats:italic>< 0.001). The results of these studies indicate that SMO is a source of bacteria-induced ROS directly associated with tumorigenesis and could serve as a unique target for chemoprevention.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380576120296145928","@type":"Researcher","foaf:name":[{"@value":"Andrew C. Goodwin"}],"jpcoar:affiliationName":[{"@value":"Departments of aOncology,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120296145927","@type":"Researcher","foaf:name":[{"@value":"Christina E. Destefano Shields"}],"jpcoar:affiliationName":[{"@value":"Departments of aOncology,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120296145923","@type":"Researcher","foaf:name":[{"@value":"Shaoguang Wu"}],"jpcoar:affiliationName":[{"@value":"Medicine,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120296145930","@type":"Researcher","foaf:name":[{"@value":"David L. Huso"}],"jpcoar:affiliationName":[{"@value":"Molecular and Comparative Pathobiology, and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120296145924","@type":"Researcher","foaf:name":[{"@value":"XinQun Wu"}],"jpcoar:affiliationName":[{"@value":"Medicine,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120296145922","@type":"Researcher","foaf:name":[{"@value":"Tracy R. Murray-Stewart"}],"jpcoar:affiliationName":[{"@value":"Departments of aOncology,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120296145926","@type":"Researcher","foaf:name":[{"@value":"Amy Hacker-Prietz"}],"jpcoar:affiliationName":[{"@value":"Departments of aOncology,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120296145920","@type":"Researcher","foaf:name":[{"@value":"Shervin Rabizadeh"}],"jpcoar:affiliationName":[{"@value":"Pediatrics and The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21231; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120296145925","@type":"Researcher","foaf:name":[{"@value":"Patrick M. Woster"}],"jpcoar:affiliationName":[{"@value":"Department of Pharmaceutical and Biomedical Sciences, Medical Univeristy of South Carolina, Charleston, SC 29425"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120296145929","@type":"Researcher","foaf:name":[{"@value":"Cynthia L. Sears"}],"jpcoar:affiliationName":[{"@value":"Departments of aOncology,"},{"@value":"Medicine,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120296145921","@type":"Researcher","foaf:name":[{"@value":"Robert A. Casero"}],"jpcoar:affiliationName":[{"@value":"Departments of aOncology,"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"2011-08-29","prism:volume":"108","prism:number":"37","prism:startingPage":"15354","prism:endingPage":"15359"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.1010203108"}],"createdAt":"2011-08-30","modifiedAt":"2025-03-09","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360021390753354240","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Enrichment of Bacteroides fragilis and enterotoxigenic Bacteroides fragilis in CpG island methylator phenotype-high colorectal carcinoma"}]},{"@id":"https://cir.nii.ac.jp/crid/1360283692122769536","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"A Novel Putrescine Exporter SapBCDF of Escherichia coli"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848660379131904","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Host–microbe interactions via membrane transport systems"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865814756524544","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Inhibition of Polyamine Catabolism Reduces Cellular Senescence"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865815682984960","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Gut Bacteria-derived Membrane Vesicles Induce Colonic Dysplasia by Inducing DNA Damage in Colon Epithelial Cells"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1073/pnas.1010203108"},{"@type":"CROSSREF","@value":"10.1016/j.cmi.2024.01.013_references_DOI_FODmySOYVTiO8eFP2HAJBa3YU2L"},{"@type":"CROSSREF","@value":"10.1074/jbc.m116.762450_references_DOI_FODmySOYVTiO8eFP2HAJBa3YU2L"},{"@type":"CROSSREF","@value":"10.1111/1462-2920.12632_references_DOI_FODmySOYVTiO8eFP2HAJBa3YU2L"},{"@type":"CROSSREF","@value":"10.3390/ijms241713397_references_DOI_FODmySOYVTiO8eFP2HAJBa3YU2L"},{"@type":"CROSSREF","@value":"10.1016/j.jcmgh.2024.01.010_references_DOI_FODmySOYVTiO8eFP2HAJBa3YU2L"}]}