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Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite

dc.contributor.authorDuarte, D.
dc.contributor.authorAmaro, F.
dc.contributor.authorSilva, I.
dc.contributor.authorSilva, D.
dc.contributor.authorFresco, P.
dc.contributor.authorOliveira, José Carlos
dc.contributor.authorREGUENGO, HENRIQUE
dc.contributor.authorGonçalves, J.
dc.contributor.authorVale, N.
dc.date.accessioned2020-04-16T15:15:11Z
dc.date.available2020-04-16T15:15:11Z
dc.date.issued2019
dc.description.abstractCarbidopa is used for the treatment of Parkinson's disease (PD) as an inhibitor of DOPA decarboxylase, and PD patients taking carbidopa have a lower incidence of various tumors, except for breast cancer and melanoma. Recently, it was shown that carbidopa inhibits tryptophan-2,3-dioxygenase (TDO) and kynureninase enzymes. In the present study, the effect of carbidopa on the viability and metabolic profile of breast cancer MCF-7 and melanoma A375 cells was investigated. Carbidopa was not effective in inhibiting MCF-7 and A375 proliferation. Liquid chromatography and mass spectrometry revealed a new compound, identified as indole-3-acetonitrile (IAN), which promoted a concentration-dependent increase in the viability of both cell lines. The results suggest that treatment with carbidopa may alter tryptophan (Trp) metabolism in breast cancer and melanoma leading to the formation of a pro-proliferative Trp metabolite, which may contribute to its failure in reducing breast cancers and melanoma incidence in PD patients taking carbidopa.pt_PT
dc.description.sponsorshipThis work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT, in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274).” NV thanks FCT for IF position, Fundação Manuel António da Mota (FMAM, Portugal) for support. The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of the FCT and FMAMpt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationDuarte D, Amaro F, Silva I, et al. Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite. Biomolecules. 2019;9(9):409. Published 2019 Aug 24. doi:10.3390/biom9090409pt_PT
dc.identifier.doi10.3390/biom9090409pt_PT
dc.identifier.issn2218-273X
dc.identifier.urihttp://hdl.handle.net/10400.16/2355
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relation.publisherversionhttps://www.mdpi.com/2218-273X/9/9/409pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectA375 cell line; MCF-7 cell linept_PT
dc.subjectcarbidopapt_PT
dc.subjectindole-3-acetonitrilept_PT
dc.subjecttryptophanpt_PT
dc.titleCarbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolitept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceSwitzerlandpt_PT
oaire.citation.issue9pt_PT
oaire.citation.startPage409pt_PT
oaire.citation.titleBiomoleculespt_PT
oaire.citation.volume9pt_PT
person.familyNameOliveira
person.familyNameReguengo Luz
person.givenNameJosé Carlos
person.givenNameHenrique
person.identifier806053
person.identifier.ciencia-id801F-D4FE-8694
person.identifier.ciencia-idD315-6421-A327
person.identifier.orcid0000-0003-2142-6839
person.identifier.orcid0000-0002-0246-6790
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationbd6d8008-2622-4368-8ded-4ec1c1160c82
relation.isAuthorOfPublicationdc00d9fd-3fff-4a83-a190-d0111a136116
relation.isAuthorOfPublication.latestForDiscoverybd6d8008-2622-4368-8ded-4ec1c1160c82

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