title: Androgen-responsive and nonresponsive prostate cancer cells present a distinct glycolytic metabolism profile.
abstract: 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.
authors.affiliation: CICS-UBI - Health Sciences Research Center, University of Beira Interior, Av Infante D Henrique, 6200-506 Covilhã, Portugal.
authors.forename: Cátia V
authors.initials: CV
authors.lastname: Vaz
authors.forename: Marco G
authors.initials: MG
authors.lastname: Alves
authors.forename: Ricardo
authors.initials: R
authors.lastname: Marques
authors.forename: Paula I
authors.initials: PI
authors.lastname: Moreira
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Oliveira
authors.forename: Cláudio J
authors.initials: CJ
authors.lastname: Maia
authors.forename: Sílvia
authors.initials: S
authors.lastname: Socorro
mesh_terms: D000409:Alanine / Q000096:biosynthesis; D000728:Androgens / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000096:biosynthesis; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D008954:Models, Biological; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D010732:Phosphofructokinase-1 / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000728:Androgens; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D012333:RNA, Messenger; C406962:SLC16A4 protein, human; C495677:SLC2A1 protein, human; C495687:SLC2A3 protein, human; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase; D010732:Phosphofructokinase-1; D005947:Glucose; D000409:Alanine