Anti-Tumorigenic Effect of a Novel Derivative of 2-Hydroxyoleic Acid and the Endocannabinoid Anandamide on Neuroblastoma Cells

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2022 Jul 27

PMID 35884854

Authors

Hana Golan

Raphael Mechoulam

Reem Smoum

Efrat Cohen-Zada

Sara Pri-Chen

Sapir Wiener

Igor Grinberg

Dekel D Bar-Lev

Christeeneh G Haj

Tamar Fisher

Amos Toren

Affiliations

Soon will be listed here.

Abstract

Modulation of the endogenous cannabinoid system has been suggested as a potential anticancer strategy. In the search for novel and less toxic therapeutic options, structural modifications of the endocannabinoid anandamide and the synthetic derivative of oleic acid, Minerval (HU-600), were done to obtain 2-hydroxy oleic acid ethanolamide (HU-585), which is an HU-600 derivative with the anandamide side chain. We showed that treatment of SK-N-SH neuroblastoma cells with HU-585 induced a better anti-tumorigenic effect in comparison to HU-600 as evidenced by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide assay, colony-forming assay, and migration assay. Moreover, HU-585 demonstrated pro-apoptotic properties shown by increased levels of activated caspase-3 following treatment and a better senescence induction effect in comparison to HU-600, as demonstrated by increased activity of lysosomal β-galactosidase. Finally, we observed that combined treatment of HU-585 with the senolytic drugs ABT-263 in vitro, and ABT-737 in vivo resulted in enhanced anti-proliferative effects and reduced neuroblastoma xenograft growth in comparison to treatment with HU-585 alone. Based on these results, we suggest that HU-585 is a pro-apoptotic and senescence-inducing compound, better than HU-600. Hence, it may be a beneficial option for the treatment of resistant neuroblastoma especially when combined with senolytic drugs that enhance its anti-tumorigenic effects.

Citing Articles

Special Issue: Therapeutic Potential for Cannabis and Cannabinoids.

Raup-Konsavage W Biomedicines. 2023; 11(3).

PMID: 36979881 PMC: 10045812. DOI: 10.3390/biomedicines11030902.

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