Application of the nuclear factor-kappaB inhibitor BAY 11-7085 for the treatment of endometriosis: an in vitro study.
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.
Nasu
Kaei
K
Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Oita, Japan. nasu@med.oita-u.ac.jp
Nishida
Masakazu
M
Ueda
Tami
T
Yuge
Akitoshi
A
Takai
Noriyuki
N
Narahara
Hisashi
H
D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004715:Endometriosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use*; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use*
C416282:BAY 11-7085; D016328:NF-kappa B; D009570:Nitriles; D013450:Sulfones