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dc.contributor.authorRashidieh, Behnam
dc.contributor.authorMolakarimi, Maryam
dc.contributor.authorMohseni, Ammar
dc.contributor.authorTria, Simon Manuel
dc.contributor.authorTruong, Hein
dc.contributor.authorSrihari, Sriganesh
dc.contributor.authorAdams, Rachael C
dc.contributor.authorJones, Mathew
dc.contributor.authorDuijf, Pascal HG
dc.contributor.authorKalimutho, Murugan
dc.contributor.authorKhanna, Kum Kum
dc.date.accessioned2021-08-15T22:41:07Z
dc.date.available2021-08-15T22:41:07Z
dc.date.issued2021
dc.identifier.issn2072-6694
dc.identifier.doi10.3390/cancers13153778
dc.identifier.urihttp://hdl.handle.net/10072/406846
dc.description.abstractThe overexpression of BRF2, a selective subunit of RNA polymerase III, has been shown to be crucial in the development of several types of cancers, including breast cancer and lung squamous cell carcinoma. Predominantly, BRF2 acts as a central redox-sensing transcription factor (TF) and is involved in rescuing oxidative stress (OS)-induced apoptosis. Here, we showed a novel link between BRF2 and the DNA damage response. Due to the lack of BRF2-specific inhibitors, through virtual screening and molecular dynamics simulation, we identified potential drug candidates that interfere with BRF2-TATA-binding Protein (TBP)-DNA complex interactions based on binding energy, intermolecular, and torsional energy parameters. We experimentally tested bexarotene as a potential BRF2 inhibitor. We found that bexarotene (Bex) treatment resulted in a dramatic decline in oxidative stress and Tert-butylhydroquinone (tBHQ)-induced levels of BRF2 and consequently led to a decrease in the cellular proliferation of cancer cells which may in part be due to the drug pretreatment-induced reduction of ROS generated by the oxidizing agent. Our data thus provide the first experimental evidence that BRF2 is a novel player in the DNA damage response pathway and that bexarotene can be used as a potential inhibitor to treat cancers with the specific elevation of oxidative stress.
dc.description.peerreviewedYes
dc.languageeng
dc.publisherMDPI AG
dc.relation.ispartofpagefrom3778
dc.relation.ispartofissue15
dc.relation.ispartofjournalCancers
dc.relation.ispartofvolume13
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchcode3211
dc.subject.keywordsBRF2
dc.subject.keywordsbexarotene
dc.subject.keywordscancer
dc.subject.keywordsdrug repurposing
dc.subject.keywordsmolecular dynamics simulation
dc.titleTargeting BRF2 in Cancer Using Repurposed Drugs
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationRashidieh, B; Molakarimi, M; Mohseni, A; Tria, SM; Truong, H; Srihari, S; Adams, RC; Jones, M; Duijf, PHG; Kalimutho, M; Khanna, KK, Targeting BRF2 in Cancer Using Repurposed Drugs., Cancers, 2021, 13 (15), pp. 3778-3778
dcterms.dateAccepted2021-07-21
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2021-08-13T00:48:51Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorKhanna, Kum K.


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