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

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-κB 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-XLexpression 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.

Hexane extract of aged black garlic reduces cell proliferation and attenuates the expression of ICAM-1 and VCAM-1 in TNF-α-activated human endometrial stromal cells

“…The canonical pathway of NF-κB is activated in endometriotic lesions, and modulation of NF-κB activity and the consequent cell responses, including proliferation, inflammation and adhesion are important in the development of endometriosis (3,13,24,25). Thus, it is noteworthy that the present study demonstrated that HEABG significantly inhibits the TNF-α-induced activation of NF-κB and AP-1 in HESCs.…”

Novel Medical Treatment Modalities of Endometriosis

“…Cell proliferation, motility, adhesion, and invasion abilities were signifi cantly reduced, and apoptosis was increased in vitro [32][33][34] . NF-kB suppression was useful in reducing endometriosis establishment and progression in animal models and diminishing endometriosis-associated symptoms in women.…”

Treatment of Endometriosis with Non-Hormonal Agents: Review

“…52 NF-κB inhibitörlerinin in vitro testlerde hücrele-rin çoğalmasını, motilitesini, adezyonunu ve invazyonunu önemli şekilde azalttığı, apoptoziste ise artışa neden olduğu izlenmiştir. 53,54 …”