Androgen-responsive and nonresponsive prostate cancer cells present a distinct glycolytic metabolism profile

Detalhes bibliográficos
Autor(a) principal: Vaz, Cátia Alexandra Vicente
Data de Publicação: 2012
Outros Autores: Alves, Marco G., Marques, Ricardo, Moreira, Paula I, Oliveira, P.F., Baptista, Cláudio, Socorro, Sílvia
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.6/7633
Resumo: Prostate cancer (PCa) progresses from an early stage, confined to prostate, to a more aggressive metastasized cancer related with loss of androgen responsiveness. Although, it has been recognized that PCa cells have unique metabolic features, their glycolytic profile in androgen-dependent and androgen-independent stages of disease is much less known. Hence, the main purpose of this study was to compare glucose metabolism in androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) PCa cells. Cell culture medium was collected and differences in glucose consumption and, lactate and alanine production were measured using Proton Nuclear Magnetic Resonance ((1)H NMR) spectra analysis. The mRNA and protein expression of glucose transporters (GLUT1 and GLUT3), phosphofructokinase 1 (PFK1), lactate dehydrogenase (LDH) and monocarboxylate transporter (MCT4) were determined by real-time PCR and Western Blot, respectively. The obtained results demonstrate that androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) cells consumed similar amounts of glucose, whereas PC3 cells present higher lactate production. This increase in lactate production was concomitant with higher levels of MCT4 protein, increased LDH activity and higher lactate/alanine ratio, also suggesting increased levels of oxidative stress in PC3 cells. However, protein levels of LDH, associated with lactate metabolism, and GLUT3, involved in glucose uptake, were decreased in PC3 comparatively with LNCaP. Androgen-responsive and nonresponsive PCa cells present distinct glycolytic metabolism profiles, which suggest that targeting LDH and MCT4 metabolic pathways may be an important step for the development of new diagnostic and therapeutic strategies in the different stages of PCa.
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spelling Androgen-responsive and nonresponsive prostate cancer cells present a distinct glycolytic metabolism profilePC3LNCaPAndrogenNMRMetabolomicsProstate cancer (PCa) progresses from an early stage, confined to prostate, to a more aggressive metastasized cancer related with loss of androgen responsiveness. Although, it has been recognized that PCa cells have unique metabolic features, their glycolytic profile in androgen-dependent and androgen-independent stages of disease is much less known. Hence, the main purpose of this study was to compare glucose metabolism in androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) PCa cells. Cell culture medium was collected and differences in glucose consumption and, lactate and alanine production were measured using Proton Nuclear Magnetic Resonance ((1)H NMR) spectra analysis. The mRNA and protein expression of glucose transporters (GLUT1 and GLUT3), phosphofructokinase 1 (PFK1), lactate dehydrogenase (LDH) and monocarboxylate transporter (MCT4) were determined by real-time PCR and Western Blot, respectively. The obtained results demonstrate that androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) cells consumed similar amounts of glucose, whereas PC3 cells present higher lactate production. This increase in lactate production was concomitant with higher levels of MCT4 protein, increased LDH activity and higher lactate/alanine ratio, also suggesting increased levels of oxidative stress in PC3 cells. However, protein levels of LDH, associated with lactate metabolism, and GLUT3, involved in glucose uptake, were decreased in PC3 comparatively with LNCaP. Androgen-responsive and nonresponsive PCa cells present distinct glycolytic metabolism profiles, which suggest that targeting LDH and MCT4 metabolic pathways may be an important step for the development of new diagnostic and therapeutic strategies in the different stages of PCa.uBibliorumVaz, Cátia Alexandra VicenteAlves, Marco G.Marques, RicardoMoreira, Paula IOliveira, P.F.Baptista, CláudioSocorro, Sílvia2019-11-27T17:07:57Z2012-112012-11-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.6/7633eng10.1016/j.biocel.2012.08.013metadata only accessinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-12-15T09:47:08Zoai:ubibliorum.ubi.pt:10400.6/7633Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:48:06.514812Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Androgen-responsive and nonresponsive prostate cancer cells present a distinct glycolytic metabolism profile
title Androgen-responsive and nonresponsive prostate cancer cells present a distinct glycolytic metabolism profile
spellingShingle Androgen-responsive and nonresponsive prostate cancer cells present a distinct glycolytic metabolism profile
Vaz, Cátia Alexandra Vicente
PC3
LNCaP
Androgen
NMR
Metabolomics
title_short Androgen-responsive and nonresponsive prostate cancer cells present a distinct glycolytic metabolism profile
title_full Androgen-responsive and nonresponsive prostate cancer cells present a distinct glycolytic metabolism profile
title_fullStr Androgen-responsive and nonresponsive prostate cancer cells present a distinct glycolytic metabolism profile
title_full_unstemmed Androgen-responsive and nonresponsive prostate cancer cells present a distinct glycolytic metabolism profile
title_sort Androgen-responsive and nonresponsive prostate cancer cells present a distinct glycolytic metabolism profile
author Vaz, Cátia Alexandra Vicente
author_facet Vaz, Cátia Alexandra Vicente
Alves, Marco G.
Marques, Ricardo
Moreira, Paula I
Oliveira, P.F.
Baptista, Cláudio
Socorro, Sílvia
author_role author
author2 Alves, Marco G.
Marques, Ricardo
Moreira, Paula I
Oliveira, P.F.
Baptista, Cláudio
Socorro, Sílvia
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv uBibliorum
dc.contributor.author.fl_str_mv Vaz, Cátia Alexandra Vicente
Alves, Marco G.
Marques, Ricardo
Moreira, Paula I
Oliveira, P.F.
Baptista, Cláudio
Socorro, Sílvia
dc.subject.por.fl_str_mv PC3
LNCaP
Androgen
NMR
Metabolomics
topic PC3
LNCaP
Androgen
NMR
Metabolomics
description Prostate cancer (PCa) progresses from an early stage, confined to prostate, to a more aggressive metastasized cancer related with loss of androgen responsiveness. Although, it has been recognized that PCa cells have unique metabolic features, their glycolytic profile in androgen-dependent and androgen-independent stages of disease is much less known. Hence, the main purpose of this study was to compare glucose metabolism in androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) PCa cells. Cell culture medium was collected and differences in glucose consumption and, lactate and alanine production were measured using Proton Nuclear Magnetic Resonance ((1)H NMR) spectra analysis. The mRNA and protein expression of glucose transporters (GLUT1 and GLUT3), phosphofructokinase 1 (PFK1), lactate dehydrogenase (LDH) and monocarboxylate transporter (MCT4) were determined by real-time PCR and Western Blot, respectively. The obtained results demonstrate that androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) cells consumed similar amounts of glucose, whereas PC3 cells present higher lactate production. This increase in lactate production was concomitant with higher levels of MCT4 protein, increased LDH activity and higher lactate/alanine ratio, also suggesting increased levels of oxidative stress in PC3 cells. However, protein levels of LDH, associated with lactate metabolism, and GLUT3, involved in glucose uptake, were decreased in PC3 comparatively with LNCaP. Androgen-responsive and nonresponsive PCa cells present distinct glycolytic metabolism profiles, which suggest that targeting LDH and MCT4 metabolic pathways may be an important step for the development of new diagnostic and therapeutic strategies in the different stages of PCa.
publishDate 2012
dc.date.none.fl_str_mv 2012-11
2012-11-01T00:00:00Z
2019-11-27T17:07:57Z
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