Prostaglandin D-ethanolamide induces skin cancer apoptosis by suppressing the activity of cellular antioxidants.

Prostaglandin D-ethanolamide induces skin cancer apoptosis by suppressing the activity of cellular antioxidants.

Publication date: Mar 08, 2019

The combined incidence of melanoma and non-melanoma skin cancer (NMSC) is greater than the incidence of all other malignancies in the US. Previously, we demonstrated that the endocannabinoid, arachidonoyl-ethanolamide (AEA), was a potent inducer of apoptosis in NMSC. The metabolism of AEA to the prostaglandin, PGD-EA, was a prerequisite for AEA cytotoxicity. However, the mechanism of PGD-EA cell death has not been clearly defined. In the present study, we report that PGD-EA causes apoptosis in melanoma and NMSC cells. Mass spectrometry analysis revealed that PGD-EA was dehydrated to three J-series prostaglandins; PGJ-EA, ΔPGJ-EA, and 15deoxy,Δ PGJ-EA. PGD-EA inhibited the antioxidant activity of glutathione and thioredoxin which then caused oxidative stress. This increase in oxidative stress was accompanied by the activation of endoplasmic reticulum (ER) stress and apoptosis. The effect of PGD-EA was independent of DP1, DP2, and PPARγ receptors suggesting that PGD-EA cytotoxicity was mediated by its metabolic product, 15dPGJ-EA.

Elhassanny, A.E.M., Ladin, D.A., Soliman, E., Albassam, H., Morris, A., Kobet, R., Thayne, K., Burns, C., Danell, A.S., and Van Dross, R. Prostaglandin D-ethanolamide induces skin cancer apoptosis by suppressing the activity of cellular antioxidants. 21946. 2019 Prostaglandins Other Lipid Mediat.

Concepts Keywords
Antioxidant Apoptosis
Antioxidants Peroxisome proliferator-activated receptor
Apoptosis Thioredoxin
Cytotoxicity Endocannabinoid system
Endocannabinoid Glutathione
Endoplasmic Reticulum Prostaglandins
ER Stress Branches of biology
Glutathione Metabolic product
Incidence
Inducer
Malignancies
Mass Spectrometry
Melanoma
Metabolic Product
Metabolism
Oxidative Stress
PPAR
Prostaglandin
Prostaglandins
Receptors
Thioredoxin

Semantics

Type Source Name
gene UNIPROT PPARA
gene UNIPROT TFDP2
gene UNIPROT PTGDR2
gene UNIPROT APC
gene UNIPROT TFDP1
gene UNIPROT REEP5
gene UNIPROT PTGDR
pathway BSID Oxidative Stress
disease MESH oxidative stress
drug DRUGBANK Thioredoxin
drug DRUGBANK Glutathione
gene UNIPROT FBN1
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
gene UNIPROT PGD
gene UNIPROT PHGDH
pathway BSID Metabolism
disease MESH malignancies
pathway BSID Apoptosis
disease DOID skin cancer
disease MESH skin cancer

Original Article

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