Canna~Fangled Abstracts

The Endocannabinoid System as a Pharmacological Target for New Cancer Therapies

By November 15, 2021November 29th, 2021No Comments
Review
. 2021 Nov 15;13(22):5701.

doi: 10.3390/cancers13225701.

Robert Ramer 1, Felix Wittig 1, Burkhard Hinz 1
Affiliations 

Abstract

Despite the long history of cannabinoid use for medicinal and ritual purposes, an endogenous system of cannabinoid-controlled receptors, as well as their ligands and the enzymes that synthesise and degrade them, was only discovered in the 1990s. Since then, the endocannabinoid system has attracted widespread scientific interest regarding new pharmacological targets in cancer treatment among other reasons. Meanwhile, extensive preclinical studies have shown that cannabinoids have an inhibitory effect on tumour cell proliferation, tumour invasion, metastasis, angiogenesis, chemoresistance and epithelial-mesenchymal transition (EMT) and induce tumour cell apoptosis and autophagy as well as immune response. Appropriate cannabinoid compounds could moreover be useful for cancer patients as potential combination partners with other chemotherapeutic agents to increase their efficacy while reducing unwanted side effects. In addition to the direct activation of cannabinoid receptors through the exogenous application of corresponding agonists, another strategy is to activate these receptors by increasing the endocannabinoid levels at the corresponding pathological hotspots. Indeed, a number of studies accordingly showed an inhibitory effect of blockers of the endocannabinoid-degrading enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) on tumour development and spread. This review summarises the relevant preclinical studies with FAAH and MAGL inhibitors compared to studies with cannabinoids and provides an overview of the regulation of the endocannabinoid system in cancer.

 

Keywords: FAAH inhibitors, MAGL inhibitors, angiogenesis, apoptosis, autophagy, cancer, cannabinoids, endocannabinoid system, metastasis, tumour cell invasion, tumour cell proliferation, tumour-immune interactions

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Figure 2

References

    1. Devane: W.A., Hanus L., Breuer A., Pertwee R.G., Stevenson L.A., Griffin G., Gibson D., Mandelbaum A., Etinger A., Mechoulam R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992;258:1946–1949. doi: 10.1126/science.1470919. – DOI – PubMed
    1. Mechoulam R., Ben-Shabat S., Hanus L., Ligumsky M., Kaminski N.E., Schatz A.R., Gopher A., Almog S., Martin B.R., Compton D.R., et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol. 1995;50:83–90. doi: 10.1016/0006-2952(95)00109-D. – DOI – PubMed
    1. Hanus L., Abu-Lafi S., Fride E., Breuer A., Vogel Z., Shalev D.E., Kustanovich I., Mechoulam R. 2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc. Natl. Acad. Sci. USA. 2001;98:3662–3665. doi: 10.1073/pnas.061029898. – DOI – PMC – PubMed
    1. Bisogno T., Melck D., Bobrov M.Y., Gretskaya N.M., Bezuglov V.V., De Petrocellis L., Di Marzo V. N-acyl-dopamines: Novel synthetic CB1 cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo. Biochem. J. 2000;351:817–824. doi: 10.1042/bj3510817. – DOI – PMC – PubMed
    1. Porter A.C., Sauer J.M., Knierman M.D., Becker G.W., Berna M.J., Bao J., Nomikos G.G., Carter P., Bymaster F.P., Leese A.B., et al. Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J. Pharmacol. Exp. Ther. 2002;301:1020–1024. doi: 10.1124/jpet.301.3.1020. – DOI – PubMed

Publication types

Leave a Reply