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Androgens and low density lipoprotein-cholesterol interplay in modulating prostate cancer cell fate and metabolism

2022-12Journal article Open Access
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dc.contributor.authorCardoso, Henrique J.
dc.contributor.authorFigueira, Marília I.
dc.contributor.authorCarvalho, Tiago M.A.
dc.contributor.authorSerra, Catarina D.M.
dc.contributor.authorVaz, Cátia V.
dc.contributor.authorMadureira, Patricia
dc.contributor.authorSocorro, Sílvia
dc.date.accessioned2023-01-30T15:50:44Z
dc.date.available2023-01-30T15:50:44Z
dc.date.issued2022-12
dc.description.abstractBackground: Androgens, the known drivers of prostate cancer (PCa), have been indicated as important metabolic regulators with a relevant role in stimulating lipid metabolism. Also, the relationship between obesity and the aggressiveness of PCa has been established. However, it is unknown if the androgenic hormonal environment may alter the response of PCa cells to lipid availability. Purpose: The present study evaluated the effect of 5 alpha-dihydrotestosterone (DHT) in regulating lipid metabolism, and the interplay between this hormone and low-density lipoprotein (LDL)-cholesterol in modulating PCa cells fate.Methods: Non-neoplastic and neoplastic PCa cells were treated with 10 nM DHT, and the expression of fatty acids transporter, fatty acid synthase (FASN), and carnitine palmitoyltransferase 1A (CPT1A) evaluated. PCa cells were also exposed to LDL (100 mu g/ml) in the presence or absence of DHT.Results: Treatment with DHT upregulated the expression of FASN and CPT1A in androgen-sensitive PCa cells. In contrast, LDL supplementation suppressed FASN expression regardless of the presence of DHT, whereas aug-menting CPT1A levels. Our results also showed that LDL-cholesterol increased PCa cells viability, proliferation, and migration dependently on the presence of DHT. Moreover, LDL and DHT synergistically enhanced the accumulation of lipid droplets in PCa cells.Conclusions: The obtained results show that androgens deregulate lipid metabolism and enhance the effects of LDL increasing PCa cells viability, proliferation and migration. The present findings support clinical data linking obesity with PCa and first implicate androgens in this relationship. Also, they sustain the application of phar-macological approaches targeting cholesterol availability and androgens signaling simultaneously.pt_PT
dc.description.sponsorshipIF/00614/2014/CP12340006
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.prp.2022.154181pt_PT
dc.identifier.eissn1618-0631
dc.identifier.urihttp://hdl.handle.net/10400.1/18964
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationIdentification and characterization of redox regulatory proteins involved in cancer progression
dc.relationEstrogens and prostate cancer: role of GPER and regulation of stem cell factor SCF/c-KIT system
dc.relationAndrogens/anti-androgens and glycaemia in reprogramming metabolism of prostate cancer: targeting both androgen receptor and metabolism as a therapeutic option
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAndrogenspt_PT
dc.subjectLDL-cholesterolpt_PT
dc.subjectLipid metabolismpt_PT
dc.subjectProstate cancerpt_PT
dc.subjectFatty acid synthasept_PT
dc.subjectObesitypt_PT
dc.titleAndrogens and low density lipoprotein-cholesterol interplay in modulating prostate cancer cell fate and metabolismpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleIdentification and characterization of redox regulatory proteins involved in cancer progression
oaire.awardTitleEstrogens and prostate cancer: role of GPER and regulation of stem cell factor SCF/c-KIT system
oaire.awardTitleAndrogens/anti-androgens and glycaemia in reprogramming metabolism of prostate cancer: targeting both androgen receptor and metabolism as a therapeutic option
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F00614%2F2014%2FCP1234%2FCT0006/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F104671%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POR_CENTRO/SFRH%2FBD%2F111351%2F2015/PT
oaire.citation.startPage154181pt_PT
oaire.citation.titlePathology - Research and Practicept_PT
oaire.citation.volume240pt_PT
oaire.fundingStreamInvestigador FCT
oaire.fundingStreamPOR_CENTRO
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/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
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.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication.latestForDiscoverya40de6a3-d52d-45dd-8620-cb94a22ebc8f
relation.isProjectOfPublication0fdc8db0-1836-46ab-8857-73c19cba688c
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