title: Regulation of inflammation by the NF-κB pathway in ovarian cancer stem cells.
abstract: OBJECTIVE
  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 GI(50) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics Gynecology and Reproductive Sciences, Yale University, New Haven, CT 06520, USA.
authors.forename: Aliza L
authors.initials: AL
authors.lastname: Leizer
authors.forename: Ayesha B
authors.initials: AB
authors.lastname: Alvero
authors.forename: Han Hsuan
authors.initials: HH
authors.lastname: Fu
authors.forename: Jennie C
authors.initials: JC
authors.lastname: Holmberg
authors.forename: Yung-Chi
authors.initials: YC
authors.lastname: Cheng
authors.forename: Dan-Arin
authors.initials: DA
authors.lastname: Silasi
authors.forename: Thomas
authors.initials: T
authors.lastname: Rutherford
authors.forename: Gil
authors.initials: G
authors.lastname: Mor
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics
chemical_list: D016207:Cytokines; D004224:Diterpenes; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C516552:eriocalyxin B; D020169:Caspases
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