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N -Acyl Dopamines Induce Apoptosis in Endometrial Stromal Cells from Patients with Endometriosis.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Sep 30; Vol. 22 (19). Date of Electronic Publication: 2021 Sep 30. - Publication Year :
- 2021
-
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.
- Subjects :
- Caspase 3 metabolism
Caspase 9 metabolism
Cell Survival drug effects
Cells, Cultured
Dopamine pharmacology
Endometriosis pathology
Endometrium drug effects
Female
Humans
Membrane Potential, Mitochondrial drug effects
Reactive Oxygen Species metabolism
Signal Transduction drug effects
Stromal Cells drug effects
Apoptosis drug effects
Arachidonic Acids pharmacology
Dopamine analogs & derivatives
Endometriosis metabolism
Endometrium metabolism
Stromal Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34638988
- Full Text :
- https://doi.org/10.3390/ijms221910648