Acute L-glutamine deprivation compromises VEGF-a upregulation in A549/8 human carcinoma cells.

Abstract:

:Tumor ischemia participates in angiogenesis and cancer progression through cellular responses to hypoxia and nutrient deprivation. However, the contribution of amino acids limitation to this process remains poorly understood. Using serum-free cell culture conditions, we tested the impact of L-glutamine deprivation on metabolic and angiogenic responses in A549/8 carcinoma cells. In these cells, lowering glutamine concentration modified the cell cycle distribution and significantly induced apoptosis/necrosis. Although glutamine deprivation led to a HIF-independent increase in VEGF-A mRNA, the corresponding protein level remained low and correlated with the inhibition of protein synthesis and activation of the GCN2/eIF2alpha pathway. Limitation of glutamine availability also hampers hypoxia- and hypoglycemia-induced VEGF-A protein upregulation. Thus, glutamine deprivation may have no direct effect on VEGF-dependent angiogenesis, compared to hypoxia or to glucose deprivation, and may instead be detrimental to cancer progression by antagonizing ischemia-induced stresses.

journal_name

J Cell Physiol

authors

Drogat B,Bouchecareilh M,North S,Petibois C,Déléris G,Chevet E,Bikfalvi A,Moenner M

doi

10.1002/jcp.21044

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

463-72

issue

2

eissn

0021-9541

issn

1097-4652

journal_volume

212

pub_type

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