Mullerian Inhibiting Substance Suppresses Proliferation and Induces Apoptosis and Autophagy in Endometriosis Cells In Vitro

Abstract

Objective. To determine the effects of Mullerian inhibiting substance (MIS) treatment on endometriosis cells through study of apoptosis and autophagy. Design. Experimental in vitro study. Setting. University research laboratory. Cell Line. CRL-7566 endometriosis cell line. This line was established from a benign ovarian cyst taken from a patient with endometriosis. Interventions. In vitro treatment with MIS. Main Outcome Measures. The main outcome measures were cellular viability, proliferation, cell-cycle arrest, and induction of apoptosis and autophagy in endometriotic cells. Results. MIS treatment inhibited proliferation of endometriosis cells and induced apoptosis, as indicated by Annexin V staining, and induced caspase-9 cleavage and cell-cycle arrest, as evidenced by increased expression of p27 CDK-inhibitor. MIS treatment also induced autophagy in endometriosis cells as demonstrated by a significant increase in LC3-II induction, a hallmark of autophagy. Conclusions. MIS inhibits cell growth and induces autophagy, as well as apoptosis, in ectopic endometrial cell lines. Our results suggest that MIS may have a potential as a novel approach for medical treatment of endometriosis. Further studies may be needed to test the efficacy of MIS treatment in animal models and to develop MIS treatment specifically targeted to the endometriosis.

The oil-resin of the tropical rainforest tree Copaifera langsdorffii reduces cell viability, changes cell morphology and induces cell death in human endometriotic stromal cultures

“…We observed that NanoCOR exerted a stronger effect on EctESC cultures than in EuESC and CESC cultures (Figure ). In accordance with these findings, other studies have shown that stromal cells from endometriotic lesions are more susceptible to pharmacological treatment than the cultures of human stromal cells of eutopic endometrium [55–57]. Moreover, differences were also observed between the responses of EuESC and CESC cultures after treatment with NanoCOR, where the EuESC cultures better responded to the treatment (Figures and ).…”

Mesenchymal Stromal Cells Support Endometriotic Stromal CellsIn Vitro

“…The annexin V assay was used to analyze apoptosis, as previously described [ 18 ], of ESC endo and ESC cyst , which were stained with CFSE as described above before they were added to 12-well plates and cultured with irradiated Ad-MSC. After 3 days of cell culture, ESC endo and ESC cyst were harvested and resuspended in 100 μ L annexin V binding buffer (10 mM of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (Life technologies) + 140 mM of sodium chloride (Sigma) + 2.5 mM of calcium chloride (Sigma)).…”

Müllerian inhibiting substance inhibits an ovarian cancer cell line via β-catenin interacting protein deregulation of the Wnt signal pathway

“…ICAT inhibits ovarian cancer cell proliferation and invasion, by inducing cell apoptosis and arrests cell cycle progression (28). MIS/AMH inhibits cell growth and induces autophagy in gynecological cancer cell lines (29). A recent study shows that MIS/AMH-treated cells accumulated in the G 1 phase of the cell cycle and subsequently underwent apoptosis in human epithe-lial ovarian cancer cells.…”