Cannabinoids, endocannabinoids, and cancer

Daniel J Hermanson, Lawrence J Marnett, Daniel J Hermanson, Lawrence J Marnett

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.

Figures

Figure 1. Biosynthesis of AEA
Figure 1. Biosynthesis of AEA
NAT catalyzes the transfer of AA from PC to the ethanolamine of PE to from NAPE. NAPE is then hydrolyzed by NAPE-PLD to form AEA.
Figure 2. Biosynthesis of 2-AG
Figure 2. Biosynthesis of 2-AG
PIP2 is hydrolyzed by PLC-β to form DAG. DAGL then hydrolyzes DAG to form 2-AG.
Figure 3. Metabolism of 2-AG and AEA
Figure 3. Metabolism of 2-AG and AEA
The endocannabinoids are primarily metabolized by hydrolysis to AA. 2-AG is hydrolyzed by MAGL and AEA is hydrolyzed by FAAH.
Figure 4
Figure 4
Structures of compounds used to study the endocannabinoid system.

Source: PubMed

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