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Article: Anticancer auranofin engages 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) as a target

TitleAnticancer auranofin engages 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) as a target
Authors
Keywordsantineoplastic activity
apoptosis
bioinformatics
cell fractionation
controlled study
Issue Date2019
PublisherRoyal Society of Chemistry. The Journal's web site is located at http://www.rsc.org/Publishing/Journals/MT/About.asp
Citation
Metallomics, 2019, v. 11 n. 11, p. 1925-1936 How to Cite?
AbstractAuranofin (AuRF) has been reported to display anticancer activity and has entered several clinical trials; however, its mechanism of action remains largely unknown. In this work, the anticancer mechanism of auranofin was investigated using a proteomics strategy entailing subcellular fractionation prior to mass spectrometric analysis. Bioinformatics analysis of the nuclear sub-proteomes revealed that tumor suppressor p14ARF is a key regulator of transcription. Through independent analysis, we validated that up-regulation of p14ARF is associated with E2F-dependent transcription and increased p53 expression. Our analyses further reveal that 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), which is the rate-determining enzyme of the mevalonate pathway, is a novel target of auranofin with half maximal inhibitory concentration at micromolar levels. The auranofin-induced cancer cell death could be partially reverted by the addition of downstream products of the mevalonate pathway (mevalonolactone or geranyleranyl pyrophosphate (GGPP)), implying that auranofin may target the mevalonate pathway to exert its anticancer effect.
Persistent Identifierhttp://hdl.handle.net/10722/282883
ISSN
2019 Impact Factor: 3.796
2015 SCImago Journal Rankings: 1.120

 

DC FieldValueLanguage
dc.contributor.authorTian, S-
dc.contributor.authorSiu, FM-
dc.contributor.authorLok, CN-
dc.contributor.authorFung, YME-
dc.contributor.authorChe, CM-
dc.date.accessioned2020-06-05T06:22:41Z-
dc.date.available2020-06-05T06:22:41Z-
dc.date.issued2019-
dc.identifier.citationMetallomics, 2019, v. 11 n. 11, p. 1925-1936-
dc.identifier.issn1756-5901-
dc.identifier.urihttp://hdl.handle.net/10722/282883-
dc.description.abstractAuranofin (AuRF) has been reported to display anticancer activity and has entered several clinical trials; however, its mechanism of action remains largely unknown. In this work, the anticancer mechanism of auranofin was investigated using a proteomics strategy entailing subcellular fractionation prior to mass spectrometric analysis. Bioinformatics analysis of the nuclear sub-proteomes revealed that tumor suppressor p14ARF is a key regulator of transcription. Through independent analysis, we validated that up-regulation of p14ARF is associated with E2F-dependent transcription and increased p53 expression. Our analyses further reveal that 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), which is the rate-determining enzyme of the mevalonate pathway, is a novel target of auranofin with half maximal inhibitory concentration at micromolar levels. The auranofin-induced cancer cell death could be partially reverted by the addition of downstream products of the mevalonate pathway (mevalonolactone or geranyleranyl pyrophosphate (GGPP)), implying that auranofin may target the mevalonate pathway to exert its anticancer effect.-
dc.languageeng-
dc.publisherRoyal Society of Chemistry. The Journal's web site is located at http://www.rsc.org/Publishing/Journals/MT/About.asp-
dc.relation.ispartofMetallomics-
dc.subjectantineoplastic activity-
dc.subjectapoptosis-
dc.subjectbioinformatics-
dc.subjectcell fractionation-
dc.subjectcontrolled study-
dc.titleAnticancer auranofin engages 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) as a target-
dc.typeArticle-
dc.identifier.emailLok, CN: cnlok@hkucc.hku.hk-
dc.identifier.emailFung, YME: eva.fungym@hku.hk-
dc.identifier.emailChe, CM: chemhead@hku.hk-
dc.identifier.authoritySiu, FM=rp00776-
dc.identifier.authorityLok, CN=rp00752-
dc.identifier.authorityFung, YME=rp01986-
dc.identifier.authorityChe, CM=rp00670-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1039/C9MT00185A-
dc.identifier.pmid31631207-
dc.identifier.scopuseid_2-s2.0-85074962973-
dc.identifier.hkuros310309-
dc.identifier.volume11-
dc.identifier.issue11-
dc.identifier.spage1925-
dc.identifier.epage1936-
dc.publisher.placeUnited Kingdom-

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