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Article: Glutathione and Thioredoxin Antioxidant Pathways Synergize to Drive Cancer Initiation and Progression

TitleGlutathione and Thioredoxin Antioxidant Pathways Synergize to Drive Cancer Initiation and Progression
Authors
Issue Date2015
PublisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/ccell
Citation
Cancer Cell, 2015, v. 27 n. 2, p. 211-222 How to Cite?
AbstractControversy over the role of antioxidants in cancer has persisted for decades. Here, we demonstrate that synthesis of the antioxidant glutathione (GSH), driven by GCLM, is required for cancer initiation. Genetic loss of Gclm prevents a tumor’s ability to drive malignant transformation. Intriguingly, these findings can be replicated using an inhibitor of GSH synthesis, but only if delivered prior to cancer onset, suggesting that at later stages of tumor progression GSH becomes dispensable potentially due to compensation from alternative antioxidant pathways. Remarkably, combined inhibition of GSH and thioredoxin antioxidant pathways leads to a synergistic cancer cell death in vitro and in vivo, demonstrating the importance of these two antioxidants to tumor progression and as potential targets for therapeutic intervention.
Persistent Identifierhttp://hdl.handle.net/10722/212130
ISSN
2020 Impact Factor: 31.743
2020 SCImago Journal Rankings: 13.035
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHarris, IS-
dc.contributor.authorTreloar, AE-
dc.contributor.authorInoue, S-
dc.contributor.authorSasaki, M-
dc.contributor.authorGorrini, C-
dc.contributor.authorLee, KC-
dc.contributor.authorYung, KY-
dc.contributor.authorBrenner, D-
dc.contributor.authorKnobbe-Thomsen, CB-
dc.contributor.authorCox, MA-
dc.contributor.authorElia, A-
dc.contributor.authorBerger, T-
dc.contributor.authorCescon, DW-
dc.contributor.authorAdeoye, A-
dc.contributor.authorBrüstle, A-
dc.contributor.authorMolyneux, SD-
dc.contributor.authorMason, JM-
dc.contributor.authorLi, WY-
dc.contributor.authorYamamoto, K-
dc.contributor.authorWakeham, A-
dc.contributor.authorBerman, HK-
dc.contributor.authorKhokha, R-
dc.contributor.authorDone, SJ-
dc.contributor.authorKavanagh, TJ-
dc.contributor.authorLam, CW-
dc.contributor.authorMak, TW-
dc.date.accessioned2015-07-21T02:24:07Z-
dc.date.available2015-07-21T02:24:07Z-
dc.date.issued2015-
dc.identifier.citationCancer Cell, 2015, v. 27 n. 2, p. 211-222-
dc.identifier.issn1535-6108-
dc.identifier.urihttp://hdl.handle.net/10722/212130-
dc.description.abstractControversy over the role of antioxidants in cancer has persisted for decades. Here, we demonstrate that synthesis of the antioxidant glutathione (GSH), driven by GCLM, is required for cancer initiation. Genetic loss of Gclm prevents a tumor’s ability to drive malignant transformation. Intriguingly, these findings can be replicated using an inhibitor of GSH synthesis, but only if delivered prior to cancer onset, suggesting that at later stages of tumor progression GSH becomes dispensable potentially due to compensation from alternative antioxidant pathways. Remarkably, combined inhibition of GSH and thioredoxin antioxidant pathways leads to a synergistic cancer cell death in vitro and in vivo, demonstrating the importance of these two antioxidants to tumor progression and as potential targets for therapeutic intervention.-
dc.languageeng-
dc.publisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/ccell-
dc.relation.ispartofCancer Cell-
dc.titleGlutathione and Thioredoxin Antioxidant Pathways Synergize to Drive Cancer Initiation and Progression-
dc.typeArticle-
dc.identifier.emailLee, KC: lee1983@hku.hk-
dc.identifier.emailLam, CW: ching-wanlam@pathology.hku.hk-
dc.identifier.emailMak, TW: tmak@uhnres.utoronto.ca-
dc.identifier.authorityLam, CW=rp00260-
dc.identifier.authorityMak, TW=rp02746-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1016/j.ccell.2014.11.019-
dc.identifier.pmid25620030-
dc.identifier.scopuseid_2-s2.0-84922783167-
dc.identifier.hkuros245380-
dc.identifier.volume27-
dc.identifier.issue2-
dc.identifier.spage211-
dc.identifier.epage222-
dc.identifier.isiWOS:000349515200009-
dc.publisher.placeUnited States-
dc.identifier.issnl1535-6108-

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