Cancer and Metastasis Reviews

, Volume 30, Issue 3–4, pp 599–612 | Cite as

Cannabinoids, endocannabinoids, and cancer

Article

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.

Keywords

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

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

Notes

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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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt Ingram Comprehensive Cancer CenterVanderbilt University School of MedicineNashvilleUSA

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