Application of the nuclear factor-κB inhibitor BAY 11-7085 for the treatment of endometriosis: an in vitro study

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The nuclear factor-κB inhibitor BAY 11-7085 suppressed endometriotic cyst stromal cell proliferation and induced apoptosis via caspase activation and downregulation of antiapoptotic proteins.

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Abstract

Most of the current medical treatments for endometriosis aim to downregulate estrogen activity. However, a high recurrence rate after medical treatment has been the most significant problem. BAY 11-7085, a soluble inhibitor of NK-kappaB activation, has been shown to inhibit cell proliferation and induce apoptosis of a variety of cells. To examine the potential application of BAY 11-7085 in the treatment of endometriosis, we investigated the effects of this agent on the cell proliferation and apoptosis of cultured ovarian endometriotic cyst stromal cells (ECSCs) by a modified methylthiazole tetrazolium assay, a 5-bromo-2'-deoxyuridine incorporation assay, and internucleosomal DNA fragmentation assays. The effect of BAY 11-7085 on the cell cycle of ECSCs was also determined by flow cytometry. The expression of apoptosis-related molecules was examined in ECSCs with Western blot analysis. BAY 11-7085 significantly inhibited the cell proliferation and DNA synthesis of ECSCs and induced apoptosis and the G0/G1 phase cell cycle arrest of these cells. Additionally, downregulation of the B-cell lymphoma/leukemia-2 (Bcl-2) and Bcl-X(L) expression with simultaneous activation of caspase-3, -8, and -9 was observed in ECSCs after treatment with BAY 11-7085. These results suggest that BAY 11-7085 induces apoptosis of ECSCs by suppressing antiapoptotic proteins, and that caspase-3-, -8-, and -9-mediated cascades are involved in this mechanism. Therefore, BAY 11-7085 could be used as a therapeutic agent for the treatment of endometriosis.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis NF-kappa B Nitriles Sulfones Apoptosis Apoptosis Cell Cycle Cell Cycle Cell Proliferation Cell Proliferation Cells, Cultured Cell Survival Cell Survival Endometriosis Female Humans NF-kappa B Nitriles Nitriles Sulfones

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