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Cannabinoid Signaling in Glioma Cells

Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 986)

Abstract

Cannabinoids are a group of structurally heterogeneous but pharmacologically related compounds, including plant-derived cannabinoids, synthetic substances and endogenous cannabinoids, such as anandamide and 2-arachidonoylglycerol. Cannabinoids elicit a wide range of central and peripheral effects mostly mediated through cannabinoid receptors. There are two types of specific Gi/o-protein-coupled receptors cloned so far, called CB1 and CB2, although an existence of additional cannabinoid-binding receptors has been suggested. CB1 and CB2 differ in their predicted amino acid sequence, tissue distribution, physiological role and signaling mechanisms. Significant alterations of a balance in the cannabinoid system between the levels of endogenous ligands and their receptors occur during malignant transformation in various types of cancer, including gliomas. Cannabinoids exert anti-proliferative action in tumor cells. Induction of cell death by cannabinoid treatment relies on the generation of a pro-apoptotic sphingolipid ceramide and disruption of signaling pathways crucial for regulation of cellular proliferation, differentiation or apoptosis. Increased ceramide levels lead also to ER-stress and autophagy in drug-treated glioblastoma cells.

Keywords

Cannabinoids Apoptosis Autophagy ER-stress Gliomas 

Abbreviations

AEA

Anandamide, arachidonoylethanolamide

2-AG

2-Arachidonoylglycerol

Akt

Protein kinase B/Akt

ATF4

Activating transcription factor 4

cAMP

Cylic adenosine monophosphate

CB1

Cannabinoid receptor type 1

CB2

Cannabinoid receptor type 2

CHOP

The C/EBP-homologous protein

DAG

Diacylglycerol

eIF2α

Eukaryotic translation initiation factor 2α

ER

Endoplasmic reticulum

ERK1/2

Extracellular signal-regulated kinase 1/2

FAAH

Fatty acid amide hydrolase

IP3

Inositol 1,4,5-trisphosphate

LPS

Lipopolysacharide

MAPK

Mitogen-activated protein kinase

MEK

MAP kinase-ERK kinase

MGL

Monoacylglycerol lipase

mTORC1

Mammalian target of rapamycin, complex 1

NAPE

N-Arachidonylphosphatidylethanolamide

PI3K

Phosphatidylinositol 3-kinase

PIP2

Phosphatidylinositol 4,5-bisphosphate

PKA

Protein kinase A

PKC

Protein kinase C

PLC

Phospholipase C

Δ9-THC

(−)-trans9-Tetrahydrocannabinol

TRB3

Pseudo-kinase tribbles homologue 3

TRPV1

Transient receptor potential cation channel subfamily V member 1, capsaicin or vanilloid receptor

WIN55,212-2

Synthetic cannabinoid

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Laboratory of Transcription Regulation, Department of Cell BiologyNencki Institute of Experimental Biology, Polish Academy of SciencesWarsawPoland

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