Regulation of Inflammation by the NF-κB Pathway in Ovarian Cancer Stem Cells

Authors


Gil Mor, Department of Obstetrics, Gynecology and Reproductive Sciences, Reproductive Immunology Unit, Yale University School of Medicine, 333 Cedar St., LSOG 305A, New Haven, CT 06520, USA.
E-mail: gil.mor@yale.edu

Abstract

Citation Leizer AL, Alvero AB, Fu HH, Holmberg JC, Cheng Y-C, Silasi D-A, Rutherford T, Mor G. Regulation of inflammation by the NF-κB pathway in ovarian cancer stem cells. Am J Reprod Immunol 2011; 65: 438–447

Problem  The NFκB pathway is a major source of pro-inflammatory cytokines, which may contribute to cancer chemoresistance. We showed that constitutive NFκB activity is characteristic of the ovarian cancer stem cells (OCSCs). The aim of this study is to determine whether the inhibition of NFκB by Eriocalyxin B (EriB) in the OCSCs may induce cell death in otherwise chemoresistant cells.

Methods  OCSCs and mature ovarian cancer cells (mOCCs) were treated with increasing concentrations of EriB. Cell viability was measured using the Celltiter 96 assay, and caspase activity was quantified using Caspase-Glo™ assay. Cytokine levels were quantified using xMAP technology.

Results  EriB decreased the percent of viable cells in all cultures tested with GI50 of 0.5–1 μm after 48 hrs of treatment. The intracellular changes associated with EriB-induced cell death are: (i) inhibition of NF-κB activity; (ii) decreased cytokine production; (iii) activation of caspases; and (iv) down-regulation of XIAP. In addition, EriB is able to sensitize OCSCs to TNFα and FasL-mediated cell death.

Conclusion  Inhibition of the NFκB pathway induces cell death in the OCSCs. Because the OCSCs may represent the source of recurrence and chemoresistance, the use of NFκB inhibitors like EriB may prevent recurrence in patients with ovarian cancer.

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