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Effects of Arginine and Its Deprivation on Human Glioblastoma Physiology and Signaling

  • Olena Karatsai
  • Oleh Stasyk
  • Maria Jolanta RedowiczEmail author
Chapter
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Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1202)

Abstract

The observations that numerous cancers are characterized by impairment in arginine synthesis and that deficit of exogenous arginine specifically affects their growth and viability are the ground for arginine deprivation-based anticancer treatment strategy. This review addresses molecular mechanisms of the human glioblastoma cell response to arginine deprivation. Our earlier studies have shown that arginine deprivation specifically impairs glioblastoma cell motility, adhesion and invasiveness. These changes were evoked by alterations in the actin cytoskeleton organization resulting from a decreased arginylation of β-actin isoform. Moreover, deficit of arginine induces prolonged endoplasmic reticulum (ER) stress and activation of the unfolded protein response, not leading, however, to a massive apoptosis in glioblastoma cells. Our current research indicates that cell death could be augmented by other compounds such as modulators of ER stress, for example arginine analogue of plant origin, canavanine. Implication of these studies on the development of new anti-glioma metabolic therapeutic modalities are discussed.

Keywords

Actin cytoskeleton Adhesion Arginine Arginylation Glioblastoma Invasiveness Migration Signaling Therapy 

Abbreviations

ADC

arginine decarboxylase

ADI

arginine deiminase

ADT

arginine deprivation-based therapy

AFM

arginine-free medium

AGAT

arginine glycine amidinotransferase

ARG

arginase

ASL

argininosuccinate lyase

ASS

argininosuccinate synthetase

CAT

cationic amino acid transporter

CM

complete medium

ER

endoplasmic reticulum

GBM

glioblastoma multiforme

GFAP

glial fibrillary acidic protein

GFP

green fluorescent protein

LFM

lysine-free medium

NO

nitric oxide

NOS

nitric oxide synthase

ODC

ornithine decarboxylase

OTC

ornithine transcarbamylase

TCA

tricarboxylic acid cycle

UPR

unfolded protein response

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Olena Karatsai
    • 1
  • Oleh Stasyk
    • 2
  • Maria Jolanta Redowicz
    • 1
    Email author
  1. 1.Laboratory of Molecular Basis of Cell MotilityNencki Institute of Experimental Biology, Polish Academy of SciencesWarsawPoland
  2. 2.Department of Cell SignalingInstitute of Cell Biology, National Academy of Sciences of UkraineLvivUkraine

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