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Cited 684 time in webofscience Cited 761 time in scopus
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Alleviating cancer drug toxicity by inhibiting a bacterial enzyme

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dc.contributor.authorWallace B.D.-
dc.contributor.authorWang H.-
dc.contributor.authorLane K.T.-
dc.contributor.authorScott J.E.-
dc.contributor.authorOrans J.-
dc.contributor.authorKoo J.S.-
dc.contributor.authorVenkatesh M.-
dc.contributor.authorJobin C.-
dc.contributor.authorYeh L.-A.-
dc.contributor.authorMani S.-
dc.contributor.authorRedinbo M.R.-
dc.date.available2020-11-03T07:44:40Z-
dc.date.issued2010-11-
dc.identifier.issn0036-8075-
dc.identifier.issn1095-9203-
dc.identifier.urihttps://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/15517-
dc.description.abstractThe dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial β-glucuronidases that reactivate the drug in the gut. We sought to target these enzymes without killing the commensal bacteria essential for human health. Potent bacterial β-glucuronidase inhibitors were identified by high-throughput screening and shown to have no effect on the orthologous mammalian enzyme. Crystal structures established that selectivity was based on a loop unique to bacterial β-glucuronidases. Inhibitors were highly effective against the enzyme target in living aerobic and anaerobic bacteria, but did not kill the bacteria or harm mammalian cells. Finally, oral administration of an inhibitor protected mice from CPT-11-induced toxicity. Thus, drugs may be designed to inhibit undesirable enzyme activities in essential microbial symbiotes to enhance chemotherapeutic efficacy.-
dc.format.extent5-
dc.language영어-
dc.language.isoENG-
dc.publisherAMER ASSOC ADVANCEMENT SCIENCE-
dc.titleAlleviating cancer drug toxicity by inhibiting a bacterial enzyme-
dc.typeArticle-
dc.publisher.location미국-
dc.identifier.doi10.1126/science.1191175-
dc.identifier.scopusid2-s2.0-78149295964-
dc.identifier.wosid000283855700046-
dc.identifier.bibliographicCitationScience, v.330, no.6005, pp 831 - 835-
dc.citation.titleScience-
dc.citation.volume330-
dc.citation.number6005-
dc.citation.startPage831-
dc.citation.endPage835-
dc.type.docTypeArticle-
dc.description.isOpenAccessN-
dc.description.journalRegisteredClasssci-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.relation.journalResearchAreaScience & Technology - Other Topics-
dc.relation.journalWebOfScienceCategoryMultidisciplinary Sciences-
dc.subject.keywordPlus7 ethyl 10 hydroxycamptothecin-
dc.subject.keywordPlus7 ethyl 10 hydroxycamptothecin glucuronide-
dc.subject.keywordPlusantineoplastic agent-
dc.subject.keywordPlusbeta glucuronidase-
dc.subject.keywordPlusglucaro 1,5 lactam-
dc.subject.keywordPlusglycosidase inhibitor-
dc.subject.keywordPlusirinotecan-
dc.subject.keywordPlusbacterium-
dc.subject.keywordPluscancer-
dc.subject.keywordPluscell organelle-
dc.subject.keywordPluschemotherapy-
dc.subject.keywordPlusdiarrheal disease-
dc.subject.keywordPlusdrug-
dc.subject.keywordPlusenzyme activity-
dc.subject.keywordPlusfunctional morphology-
dc.subject.keywordPlushealth risk-
dc.subject.keywordPlusinhibition-
dc.subject.keywordPlusinhibitor-
dc.subject.keywordPlusmammal-
dc.subject.keywordPlusmicrobial activity-
dc.subject.keywordPlustoxicity-
dc.subject.keywordPlusaerobic bacterium-
dc.subject.keywordPlusanaerobic bacterium-
dc.subject.keywordPlusanimal experiment-
dc.subject.keywordPlusarticle-
dc.subject.keywordPluscolon cancer-
dc.subject.keywordPluscrystal structure-
dc.subject.keywordPlusdiarrhea-
dc.subject.keywordPlusdrug effect-
dc.subject.keywordPlusdrug efficacy-
dc.subject.keywordPlusdrug structure-
dc.subject.keywordPlusenzyme inhibition-
dc.subject.keywordPlushuman-
dc.subject.keywordPlushuman cell-
dc.subject.keywordPlusin vitro study-
dc.subject.keywordPlusintestine flora-
dc.subject.keywordPlusintestine injury-
dc.subject.keywordPlusmouse-
dc.subject.keywordPlusnonhuman-
dc.subject.keywordPluspriority journal-
dc.subject.keywordPlusAnimals-
dc.subject.keywordPlusAntineoplastic Agents, Phytogenic-
dc.subject.keywordPlusBacteria, Anaerobic-
dc.subject.keywordPlusCamptothecin-
dc.subject.keywordPlusCell Line, Tumor-
dc.subject.keywordPlusColon-
dc.subject.keywordPlusCrystallography, X-Ray-
dc.subject.keywordPlusDiarrhea-
dc.subject.keywordPlusDrug Evaluation, Preclinical-
dc.subject.keywordPlusEnzyme Inhibitors-
dc.subject.keywordPlusEscherichia coli-
dc.subject.keywordPlusEscherichia coli Proteins-
dc.subject.keywordPlusFemale-
dc.subject.keywordPlusGlucuronidase-
dc.subject.keywordPlusHumans-
dc.subject.keywordPlusIntestinal Mucosa-
dc.subject.keywordPlusMice-
dc.subject.keywordPlusMice, Inbred BALB C-
dc.subject.keywordPlusModels, Molecular-
dc.subject.keywordPlusProdrugs-
dc.subject.keywordPlusProtein Conformation-
dc.subject.keywordPlusBacteria (microorganisms)-
dc.subject.keywordPlusMammalia-
dc.subject.keywordPlusMus-
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Ansan Hospital (Department of Gastroenterology and Hepatology, Ansan Hospital)
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