Elsevier

Redox Biology

Volume 17, July 2018, Pages 112-127
Redox Biology

Research Paper
GLUT1 protects prostate cancer cells from glucose deprivation-induced oxidative stress

https://doi.org/10.1016/j.redox.2018.03.017Get rights and content
Under a Creative Commons license
open access

Highlights

  • Glucose deprivation carries an increase of free radicals in prostate cancer cells.

  • The androgen receptor activation after glucose deprivation proceeds with GLUT1 overproduction.

  • Treatment with hydrogen peroxide mimics the response to glucose deprivation.

  • GLUT1-overexpressing prostate cancer cells are more resistant to glucose deprivation.

  • Glutathione is more reduced in GLUT1-overexpressing cells under glucose deprivation.

Abstract

Glucose, chief metabolic support for cancer cell survival and growth, is mainly imported into cells by facilitated glucose transporters (GLUTs). The increase in glucose uptake along with tumor progression is due to an increment of facilitative glucose transporters as GLUT1. GLUT1 prevents cell death of cancer cells caused by growth factors deprivation, but there is scarce information about its role on the damage caused by glucose deprivation, which usually occurs within the core of a growing tumor. In prostate cancer (PCa), GLUT1 is found in the most aggressive tumors, and it is regulated by androgens. To study the response of androgen-sensitive and insensitive PCa cells to glucose deprivation and the role of GLUT1 on survival mechanisms, androgen-sensitive LNCaP and castration-resistant LNCaP-R cells were employed. Results demonstrated that glucose deprivation induced a necrotic type of cell death which is prevented by antioxidants. Androgen-sensitive cells show a higher resistance to cell death triggered by glucose deprivation than castration-resistant cells. Glucose removal causes an increment of H2O2, an activation of androgen receptor (AR) and a stimulation of AMP-activated protein kinase activity. In addition, glucose removal increases GLUT1 production in androgen sensitive PCa cells. GLUT1 ectopic overexpression makes PCa cells more resistant to glucose deprivation and oxidative stress-induced cell death. Under glucose deprivation, GLUT1 overexpressing PCa cells sustains mitochondrial SOD2 activity, compromised after glucose removal, and significantly increases reduced glutathione (GSH). In conclusion, androgen-sensitive PCa cells are more resistant to glucose deprivation-induced cell death by a GLUT1 upregulation through an enhancement of reduced glutathione levels.

Abbreviations

2DG
2-deoxyglcuose
AMPK
AMPK-activated protein kinase
AR
Androgen Receptor
CAT
Catalase
DHA
Dehydroascorbic Acid
G6PG
Glucose-6-phosphate dehydrogenase
GPX
Glutathione peroxidase
GSH
Reduced glutathione
GSSG
Oxidized glutathione
HTLV
Human lymphotrophic virus
NAC
n-Acetylcysteine
NAMPT
Nicotinamide phosphoribosyltransferase
PCa
Prostate Cancer
PI3K
phosphoinositide 3-kinase
PSA
Prostate Specific Antigen
OXPHOS
Oxidative phosphorylation
RIPK1
Receptor-interacting serine/threonine-protein kinase 1
SOD
Superoxide dismutase
TRX
Thioredoxin
TXNIP
Thioredoxin interacting protein

Keywords

Glut1
Prostate cancer
Glucose deprivation
Androgen receptor
Glutathione
Oxidative stress

Cited by (0)

1

Both authors contributed equally.