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

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

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 ob...

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Bibliographic Details
Published in:Biomedicines Vol. 10; no. 7; p. 1552
Main Authors: Golan, Hana, Mechoulam, Raphael, Smoum, Reem, Cohen-Zada, Efrat, Pri-Chen, Sara, Wiener, Sapir, Grinberg, Igor, Bar-Lev, Dekel D, Haj, Christeeneh G, Fisher, Tamar, Toren, Amos
Format: Journal Article
Language:English
Published: Basel MDPI AG 29-06-2022
MDPI
Subjects:
2-hydroxy oleic acid
Anandamide
anti Bcl2
Antibodies
Apoptosis
Cancer therapies
Care and treatment
Caspase-3
Cell adhesion & migration
Chemical properties
Chloride
Cytotoxicity
Development and progression
Endocannabinoid system
Endocannabinoids
Fatty acids
Fibroblasts
Health aspects
Laboratories
membrane lipid therapy
Neuroblastoma
Neuroblastoma cells
Neuromodulation
Oleic acid
Physiological aspects
Proteins
Senescence
Xenografts
β-Galactosidase
Israel
United States > US
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Summary: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.
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These authors contributed equally to this work.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines10071552