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dc.contributor.authorSadowski, Martin C
dc.contributor.authorPouwer, Rebecca H
dc.contributor.authorGunter, Jennifer H
dc.contributor.authorLubik, Amy A
dc.contributor.authorQuinn, Ronald J
dc.contributor.authorNelson, Colleen C
dc.date.accessioned2017-05-03T11:15:15Z
dc.date.available2017-05-03T11:15:15Z
dc.date.issued2014
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/10072/66666
dc.description.abstractInhibition of FASN has emerged as a promising therapeutic target in cancer, and numerous inhibitors have been investigated. However, severe pharmacological limitations have challenged their clinical testing. The synthetic FASN inhibitor triclosan, which was initially developed as a topical antibacterial agent, is merely affected by these pharmacological limitations. Yet, little is known about its mechanism in inhibiting the growth of cancer cells. Here we compared the cellular and molecular effects of triclosan in a panel of eight malignant and non-malignant prostate cell lines to the well-known FASN inhibitors C75 and orlistat, which target different partial catalytic activities of FASN. Triclosan displayed a superior cytotoxic profile with a several-fold lower IC50 than C75 or orlistat. Structure-function analysis revealed that alcohol functionality of the parent phenol is critical for inhibitory action. Rescue experiments confirmed that end product starvation was a major cause of cytotoxicity. Importantly, triclosan, C75 and orlistat induced distinct changes to morphology, cell cycle, lipid content and the expression of key enzymes of lipid metabolism, demonstrating that inhibition of different partial catalytic activities of FASN activates different metabolic pathways. These finding combined with its well-documented pharmacological safety profile make triclosan a promising drug candidate for the treatment of prostate cancer.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent3726404 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.publisherImpact Journals LLC
dc.publisher.placeUnited States
dc.publisher.urihttp://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=2433
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom9362
dc.relation.ispartofpageto9381
dc.relation.ispartofissue19
dc.relation.ispartofjournalOncotarget
dc.relation.ispartofvolume5
dc.rights.retentionY
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry not elsewhere classified
dc.subject.fieldofresearchOncology and Carcinogenesis
dc.subject.fieldofresearchcode030499
dc.subject.fieldofresearchcode1112
dc.titleThe fatty acid synthase inhibitor triclosan: repurposing an anti-microbial agent for targeting prostate cancer
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/3.0/
gro.rights.copyright© The Author(s) 2014. This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorQuinn, Ronald J.
gro.griffith.authorPouwer, Rebecca


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