Endocannabinoids modulate apoptosis in endometriosis and adenomyosis

Elif Bilgic, Elif Bilgiç, Bilgic E, Guzel E, Elif Güzel, Elif Guzel, Sevil Köse, Sevil Kose, Makbule Cisel Aydin, Makbule Aydın, Eda Karaismailoğlu, Eda Karaismailoglu, Akar I, Irem Akar, Alp Usubutün, Alp Usubutun, Usubutun A, Petek Korkusuz
Acta histochemica · 2017 · vol. 119(5) , pp. 523–532 · doi:10.1016/j.acthis.2017.05.005 · PMID:28549792 · W2619651678
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This study investigated how endocannabinoids influence the process of apoptosis in women with endometriosis and adenomyosis.

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Abstract

Adenomyosis that is a form of endometriosis is the growth of ectopic endometrial tissue within the muscular wall of the uterus (myometrium), which may cause dysmenorrhea and infertility. Endocannabinoid mediated apoptotic mechanisms of endometriosis and adenomyosis are not known. We hypothesized that the down regulation of endocannabinoid receptors and/or alteration in their regulatory enzymes may have a direct role in the pathogenesis of endometriosis and adenomyosis through apoptosis. Endocannabinoid receptors CB1 and CB2, their synthesizing and catabolizing enzymes (FAAH, NAPE-PLD, DAGL, MAGL) and the apoptotic indexes were immunohistochemically assessed in endometriotic and adenomyotic tissues. Findings were compared to normal endometrium and myometrium. Endometrial adenocarcinoma (Ishikawa) and ovarian endometriosis cyst wall stromal (CRL-7566) cell lines were furthermore cultured with or without cannabinoid receptor agonists. The IC50 value for CB1 and CB2 receptor agonists was quantified. Cannabinoid agonists on cell death were investigated by Annexin-V/Propidium iodide labeling with flow cytometry. CB1 and CB2 receptor levels decreased in endometriotic and adenomyotic tissues compared to the control group (p=0,001 and p=0,001). FAAH, NAPE-PLD, MAGL and DAGL enzyme levels decreased in endometriotic and adenomyotic tissues compared to control (p=0,001, p=0,001, p=0,001 and p=0,002 respectively). Apoptotic cell indexes both in endometriotic and adenomyotic tissues also decreased significantly, compared to the control group (p=0,001 and p=0,001). CB1 and CB2 receptor agonist mediated dose dependent fast anti-proliferative and pro-apoptotic effects were detected in Ishikawa and ovarian endometriosis cyst wall stromal cell lines (CRL-7566). Endocannabinoids are suggested to increase apoptosis mechanisms in endometriosis and adenomyosis. CB1 and CB2 antagonists can be considered as potential medical therapeutic agents for endometriosis and adenomyosis.

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Condition tags

endometriosisadenomyosis

MeSH descriptors

Adenomyosis Apoptosis Endocannabinoids Endometriosis Adenomyosis Apoptosis Apoptosis Cannabinoid Receptor Agonists Cannabinoid Receptor Agonists Cannabinoid Receptor Antagonists Cannabinoid Receptor Antagonists Cell Line Endocannabinoids Endometriosis Female Flow Cytometry Humans Inhibitory Concentration 50 Protein Binding Protein Binding

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (50)

Cited by (33)

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