Androgens enhance the glycolytic metabolism and lactate export in prostate cancer cells

envie a um amigo share this

Androgens enhance the glycolytic metabolism and lactate export in prostate cancer cells

Terça, 16.06.2015

A research team from the Health Sciences Research Centre, University of Beira Interior (CICS-UBI) recently published in the Journal of Cancer Research and Clinical Oncology a study aiming to unveil the role of androgens in regulating the glycolytic metabolism, and the production and export of lactate in human prostate cancer cells. Following a previous work demonstrating that androgen-responsive and non-responsive prostate cancer cells display distinct glycolytic profiles, the present study established androgens as modulators of target genes involved in glucose uptake, as well as in its metabolization and usage for lactate production. Androgens also enhanced the export of lactate to the extracellular medium, a characteristic of more aggressive stages of prostate cancer. The reprogramming of cell metabolism in response to androgens had a favorable impact on the survival and proliferation of tumor cells, and, thus, may represent a relevant aspect driven the development and progression of prostate cancer.

 

Authors and Affiliations:

Cátia V. Vaz,  Ricardo Marques,  Marco G. Alves,  Pedro F. Oliveira,  José E. Cavaco, Cláudio J. Maia, Sílvia Socorro

 

CICS‑UBI, Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200‑506 Covilhã, Portugal

 

Abstract:

Purpose The present study aims to investigate the role of androgens in controlling the glycolytic metabolism and lactate efflux in prostate cancer (PCa) cells.

Methods Androgen-responsive LNCaP cells were treated with 5α-dihydrotestosterone (DHT, 10 nM) for 12–48 h, and their glycolytic metabolism, lactate production and viability were analyzed. Intracellular and extracellular levels of glucose and lactate were determined spectrophotometrically, and the expression of glucose transporters (GLUT1/

GLUT3), phosphofructokinase 1, lactate dehydrogenase (LDH) and monocarboxylate transporter (MCT4) was analyzed by real-time PCR and Western blot. The enzymatic activity of LDH was determined by means of a colorimetric assay. Experiments were reproduced in androgen-nonresponsive DU145 and PC3 cells.

Results Androgens stimulated glucose consumption in LNCaP cells by increasing the expression of GLUT3, GLUT1 and PFK, which was underpinned by increased cell viability. Accordingly, lactate production by LNCaP cells was enhanced upon DHT stimulation as evidenced by the increased levels of lactate found in cell culture medium. Although LDH enzymatic activity decreased in LNCaP cells treated with DHT, the expression of MCT4 was significantly increased with androgenic treatment, which sustains the increase on lactate export. Glucose consumption and the expression of GLUTs and PFK remained unchanged in DHT-treated DU145 and PC3 cells.

Conclusions The results obtained establish androgens as modulators of glycolytic metabolism in PCa cells by stimulating glucose consumption, as well as the production  and export of lactate, which may represent a crucial issue driven prostate tumor development. These findings also highlight the importance of PCa therapies targeting AR and metabolism-related proteins.

 

Journal: Journal of Cancer Research and Clinical Oncology

 

Link: http://link.springer.com/article/10.1007/s00432-015-1992-4