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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DOI: https://doi.org/10.1007/s10555-011-9318-8