N-Acyl Dopamines Induce Apoptosis in Endometrial Stromal Cells from Patients with Endometriosis

Abstract

Endometriosis is characterized by the formation and development of endometrial tissues outside the uterus, based on an imbalance between proliferation and cell death, leading to the uncontrolled growth of ectopic foci. The potential target for the regulation of these processes is the endocannabinoid system, which was found to be involved in the migration, proliferation, and survival of tumor cells. In this paper, we investigated the effect of endocannabinoid-like compounds from the N-acyl dopamine (NADA) family on the viability of stromal cells from ectopic and eutopic endometrium of patients with ovarian endometriosis. N-arachidonoyldopamine, N-docosahexaenoyldopamine, and N-oleoyldopamine have been shown to have a five-times-more-selective cytotoxic effect on endometrioid stromal cells. To study the mechanisms of the toxic effect, inhibitory analysis, measurements of caspase-3/9 activity, reactive oxygen species, and the mitochondrial membrane potential were performed. It was found that NADA induced apoptosis via an intrinsic pathway through the CB1 receptor and downstream serine palmitoyltransferase, NO synthase activation, increased ROS production, and mitochondrial dysfunction. The higher selectivity of NADA for endometriotic stromal cells and the current lack of effective drug treatment can be considered positive factors for further research of these compounds as possible therapeutic agents against endometriosis.

Transcriptome analysis of adenomyosis eutopic endometrium reveals molecular mechanisms involved in adenomyosis-related implantation failure and pregnancy disorders

“…Particularly, downregulated histamine degradation was associated with pregnancy complications, such as diabetes, miscarriage, and trophoblastic disorders [ 41 ]; Sirtuin deficiency impaired embryo invasion and decidualization [ 42 ]; ATM-deficient dams had lower implantation rates [ 43 ]; and excessive noradrenaline inhibited decidualization, embryo, and fetal development in mice [ 44 ]. Further, impaired decidualization may be caused by aberrant stromal cell differentiation, mediated by downregulated ID1 expression, [ 45 ] stromal cell apoptosis, induced by the N-acyl dopamine family [ 46 ], or attenuation of ribonucleotide reductase signaling, which impeded decidualization and implantation in mice [ 35 ]. Finally, significant repression of TSP1 mRNA expression was linked to unexplained recurrent spontaneous abortion (URSA) [ 47 ].…”

In Vitro and In Vivo Anti-Inflammatory Effects of TEES-10®, a Mixture of Ethanol Extracts of Ligularia stenocephala Matsum. & Koidz. and Secale cereale L. Sprout, on Gingivitis and Periodontitis

“…The effect of TEES-10 ® on the generation of reactive oxygen species (ROS) in the LPS-treated PDL cells was examined. We carried out 2′,7′-dichlorofluorescein (DCF-DA) staining in accordance with a precedent study [ 39 ]. PDL cells (8 × 10 3 cells/well) were cultured for 24 h and cultured further for 24 h in the media containing LPS (1 μg/mL) with or without TEES-10 ® (50 or 100 μg/mL).…”

Endometriosis: An Inflammatory Disease That Requires New Therapeutic Options

“…In their original research, Gamisonia et al [3] investigated the effect of endocannabinoidlike compounds from the N-acyl dopamine (NADA) family on the viability of stromal cells forming ectopic and eutopic endometrium of patients with ovarian endometriosis. Their in vitro study demonstrated a dose-dependent cytotoxic effect of NADAs on stromal cells of eutopic and ectopic endometrium.…”