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Cannabinoid Signaling in Glioma Cells

  • Aleksandra Ellert-MiklaszewskaEmail author
  • Iwona A. Ciechomska
  • Bozena Kaminska
Chapter
  • 93 Downloads
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1202)

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. Beyond blocking of tumor cells proliferation cannabinoids inhibit invasiveness, angiogenesis and the stem cell-like properties of glioma cells, showing profound activity in the complex tumor microenvironment. Advances in translational research on cannabinoid signaling led to clinical investigations on the use of cannabinoids in treatments of glioblastomas.

Keywords

Cannabinoids Apoptosis Autophagy ER-stress Gliomas 

Abbreviations

2-AG

2-arachidonoylglycerol

AEA

anandamide

arachidonoylethanolamide

Akt

protein kinase B/Akt

ATF4

activating transcription factor 4

cAMP

cylic adenosine monophosphate

CB1

cannabinoid receptor type 1

CB2

cannabinoid receptor type 2

CBD

cannabidiol

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

GSC

glioma stem-like cells

IP3

inositol 1,4,5-trisphosphate

LPS

lipopolysaccharide

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

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

Δ9-THC

(−)-trans9-tetrahydro-cannabinol

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Aleksandra Ellert-Miklaszewska
    • 1
    Email author
  • Iwona A. Ciechomska
    • 1
  • Bozena Kaminska
    • 1
  1. 1.Laboratory of Molecular Neurobiology, Neurobiology Center, Nencki Institute of Experimental BiologyPolish Academy of SciencesWarsawPoland

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