Cannabinoids, endocannabinoids, and cancer

Abstract

The endocannabinoid system consists of an array of endogenously produced bioactive lipids that activate cannabinoid receptors. Although the primary focus of endocannabinoid biology has been on neurological and psychiatric effects, recent work has revealed several important interactions between the endocannabinoid system and cancer. Several different types of cancer have abnormal regulation of the endocannabinoid system that contributes to cancer progression and correlates to clinical outcomes. Modulation of the endocannabinoid system by pharmacological agents in various cancer types reveals that it can mediate antiproliferative and apoptotic effects by both cannabinoid receptor-dependent and -independent pathways. Selective agonists and antagonists of the cannabinoid receptors, inhibitors of endocannabinoid hydrolysis, and cannabinoid analogs have been utilized to probe the pathways involved in the effects of the endocannabinoid system on cancer cell apoptosis, proliferation, migration, adhesion, and invasion. The antiproliferative and apoptotic effects produced by some of these pharmacological probes reveal that the endocannabinoid system is a promising new target for the development of novel chemotherapeutics to treat cancer.

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Abbreviations

THC:

Δ9-Tetrahydrocannabinol

AEA:

Anandamide

2-AG:

2-Arachidonoylglycerol

AA:

Arachidonic acid

PC:

Phosphatidylcholine

PE:

Phosphatidylethanolamine

NAT:

N-acyl transferase

NAPE:

N-arachidonoyl-phosphatidylethanolamine

NAPE-PLD:

NAPE-specific phospholipase D

PIP2 :

Phosphatidylinositol-4,5-bisphosphate

DAG:

Diacylglycerol

PLC-β:

Phospholipase C-β

DAGL:

Diacylglycerol lipase

MAGL:

Monoacylglycerol lipase

FAAH:

Fatty acid amide hydrolase

COX-2:

Cycloxygenase-2

LOXs:

Lipoxygenases

CYP450s:

Cytochromes P450

TRPV1:

Transient receptor potential vanilloid type 1

AM-356:

Methanandamide

PGs:

Prostaglandins

PG-EAs:

Prostaglandin ethanolamides

PG-Gs:

Glycerol prostaglandins

LPI:

Lysophosphatidylinositol

EGFR:

Epidermal growth factor receptor

TGFα:

Transforming growth factor α

Met-F-AEA:

Met-fluoro-anandamide

NSCLC:

Non-small cell lung cancer

HIF-1α:

Hypoxia-inducible factor 1α

Id-3:

Inhibitor of differentiation-3

Tie-1:

Angiopoietin receptor tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1

MMP:

Matrix metalloproteinase

Ang-2:

Angiopoietin-2

PlGF:

Placental growth factor

Akt:

Protein kinase B

DEA:

Docosatetraenylethanolamide

RhoA-Rock:

RhoA/Rho-associated coiled coil-containing kinase

IgSF CAMs:

Cell adhesion molecules of the immunoglobulin superfamily

ECM:

Extracellular matrix

FAK:

Focal adhesion kinase

FRNK:

FAK-related nonkinase

IL-1:

Interleukin 1

ERK1/2:

Extracellular regulating kinases 1 and 2

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Acknowledgements

Work in the Marnett Laboratory is supported by research grants from the National Institutes of Health (CA89450, GM15431, and DA031572) and the National Foundation for Cancer Research.

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Hermanson, D.J., Marnett, L.J. Cannabinoids, endocannabinoids, and cancer. Cancer Metastasis Rev 30, 599–612 (2011). https://doi.org/10.1007/s10555-011-9318-8

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Keywords

  • Cancer
  • Arachidonic acid
  • Phosphatidylcholine
  • Phosphatidylethanolamine
  • Diacylglycerol
  • Anandamide
  • 2-arachidonoylglycerol
  • Endocannabinoids
  • CB1
  • CB2