Repository logo
 
Publication

Glutaminolysis is a metabolic route essential for survival and growth of prostate cancer cells and a target of 5 alpha-dihydrotestosterone regulation

2021-04Journal article Restricted access
Simple item page
dc.contributor.authorCardoso, Henrique J.
dc.contributor.authorFigueira, Marilia, I
dc.contributor.authorVaz, Catia V.
dc.contributor.authorCarvalho, Tiago M. A.
dc.contributor.authorBras, Luis A.
dc.contributor.authorMadureira, Patricia
dc.contributor.authorOliveira, Paulo J.
dc.contributor.authorSardao, Vilma A.
dc.contributor.authorSocorro, Silvia
dc.date.accessioned2021-09-08T10:58:10Z
dc.date.available2021-09-08T10:58:10Z
dc.date.issued2021-04
dc.description.abstractPurpose Resistance to androgen-deprivation therapies and progression to so-called castrate-resistant prostate cancer (CRPC) remain challenges in prostate cancer (PCa) management and treatment. Among other alterations, CRPC has been associated with metabolic reprogramming driven by androgens. Here, we investigated the role of androgens in regulating glutaminolysis in PCa cells and determined the relevance of this metabolic route in controlling the survival and growth of androgen-sensitive (LNCaP) and CRPC (DU145 and PC3) cells. Methods PCa cells (LNCaP, DU145 and PC3) and 3-month old rats were treated with 5 alpha-dihydrotestosterone (DHT). Alternatively, LNCaP cells were exposed to the glutaminase inhibitor BPTES, alone or in combination with the anti-androgen bicalutamide. Biochemical, Western blot and extracellular flux assays were used to evaluate the viability, proliferation, migration and metabolism of PCa cells in response to DHT treatment or glutaminase inhibition. Results We found that DHT up-regulated the expression of the glutamine transporter ASCT2 and glutaminase, both in vitro in LNCaP cells and in vivo in rat prostate cells. BPTES diminished the viability and migration of PCa cells, while increasing caspase-3 activity. CRPC cells were found to be more dependent on glutamine and more sensitive to glutaminase inhibition. BPTES and bicalutamide co-treatment had an additive effect on suppressing LNCaP cell viability. Finally, we found that inhibition of glutaminolysis differentially affected glycolysis and lipid metabolism in both androgen-sensitive and CRPC cells. Conclusion Our data reveal glutaminolysis as a central metabolic route controlling PCa cell fate and highlight the relevance of targeting glutaminase for CRPC treatment.
dc.description.sponsorshipFEDER funds through the POCI - COMPETE 2020 - Operational Programme Competitiveness and Internationalization in Axis I -Strengthening research, technological development and innovation [007491, 029114]; National Funds by the FCT-Foundation for Science and Technology [UID/Multi/00709/2013]; FCTPortuguese Foundation for Science and TechnologyEuropean Commission [SFRH/BD/111351/2015, SFRH/BD/104671/2014, IF/00614/2014/CP12340006]; FCT Investigator contract from the Foundation for Science and Technology (FCT), Portugal [IF/00614/2014]; FCT Research Center grant
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1007/s13402-020-00575-9
dc.identifier.issn2211-3428
dc.identifier.urihttp://hdl.handle.net/10400.1/17048
dc.language.isoeng
dc.peerreviewedyes
dc.publisherSPRINGER
dc.relationInternational comparisons of product supply chains in the agro-food sectors: determinants of their competitiveness and performance on EU and international markets
dc.relationHealth Sciences Research Centre
dc.relationAndrogens/anti-androgens and glycaemia in reprogramming metabolism of prostate cancer: targeting both androgen receptor and metabolism as a therapeutic option
dc.relationEstrogens and prostate cancer: role of GPER and regulation of stem cell factor SCF/c-KIT system
dc.relationIdentification and characterization of redox regulatory proteins involved in cancer progression
dc.subjectProstate cancer
dc.subjectCastrate resistance
dc.subject5 alpha-dihydrotestosterone
dc.subjectBicalutamide
dc.subjectBPTES
dc.subjectASCT2
dc.subjectGlutamine
dc.subjectGlutaminolysis
dc.subject.otherOncology; Cell Biology; Pathology
dc.titleGlutaminolysis is a metabolic route essential for survival and growth of prostate cancer cells and a target of 5 alpha-dihydrotestosterone regulation
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleInternational comparisons of product supply chains in the agro-food sectors: determinants of their competitiveness and performance on EU and international markets
oaire.awardTitleHealth Sciences Research Centre
oaire.awardTitleAndrogens/anti-androgens and glycaemia in reprogramming metabolism of prostate cancer: targeting both androgen receptor and metabolism as a therapeutic option
oaire.awardTitleEstrogens and prostate cancer: role of GPER and regulation of stem cell factor SCF/c-KIT system
oaire.awardTitleIdentification and characterization of redox regulatory proteins involved in cancer progression
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/312029/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F00709%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POR_CENTRO/SFRH%2FBD%2F111351%2F2015/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F104671%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F00614%2F2014%2FCP1234%2FCT0006/PT
oaire.citation.endPage403
oaire.citation.issue2
oaire.citation.startPage385
oaire.citation.titleCellular Oncology
oaire.citation.volume44
oaire.fundingStreamFP7
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamPOR_CENTRO
oaire.fundingStreamInvestigador FCT
person.familyNameMadureira
person.givenNamePatricia
person.identifier.ciencia-id6612-9A86-6929
person.identifier.orcid0000-0002-4856-3908
person.identifier.scopus-author-id10340140500
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccess
rcaap.typearticle
relation.isAuthorOfPublicationa40de6a3-d52d-45dd-8620-cb94a22ebc8f
relation.isAuthorOfPublication.latestForDiscoverya40de6a3-d52d-45dd-8620-cb94a22ebc8f
relation.isProjectOfPublication799bea4f-0180-4bf3-bdf5-a2e627690540
relation.isProjectOfPublication349b6f84-761b-4399-9a8b-88df3ecb5d7b
relation.isProjectOfPublicationcdc68546-9b71-46f5-b970-ddea4cc6a757
relation.isProjectOfPublication5b642f91-c11f-4f78-9907-71dcfdd6fea4
relation.isProjectOfPublication0fdc8db0-1836-46ab-8857-73c19cba688c
relation.isProjectOfPublication.latestForDiscovery799bea4f-0180-4bf3-bdf5-a2e627690540

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Cardoso2021_Article_GlutaminolysisIsAMetabolicRout.pdf
Size:
3.75 MB
Format:
Adobe Portable Document Format
Download

Collections

FCB2-Artigos (em revistas ou actas indexadas)