title: Resveratrol and acetyl-resveratrol modulate activity of VEGF and IL-8 in ovarian cancer cell aggregates via attenuation of the NF-κB protein.
abstract: BACKGROUND
  Key features of advanced ovarian cancer include metastasis via cell clusters in the abdominal cavity and increased chemoresistance. Resveratrol and derivatives of resveratrol have been shown to have antitumour properties. The purpose of this study was to investigate the effect of resveratrol and acetyl-resveratrol on 3D cell aggregates of ovarian cancer, and establish if NF-κB signalling may be a potential target.
  
  
  METHODS
  Poly-HEMA coated wells were used to produce 3D aggregates of two ovarian cancer cell lines, SKOV-3 and OVCAR-5. The aggregates were exposed to 10, 20 or 30 μM resveratrol or acetyl-resveratrol for 2, 4 or 6 days. Cell growth and metabolism were measured then ELISA, western blot and immunofluorescence were utilised to evaluate VEGF, IL-8 and NF-κB levels.
  
  
  RESULTS
  Resveratrol and acetyl-resveratrol reduced cell growth and metabolism of SKOV-3 aggregates in a dose- and time-dependent manner. After 6 days all three doses of both compounds inhibited cell growth. This growth inhibition correlated with the attenuated secretion of VEGF and a decrease of NF-κB protein levels. Conversely, the secretion of IL-8 increased with treatment. The effects of the compounds were limited in OVCAR-5 cell clusters.
  
  
  CONCLUSIONS
  The results suggest that resveratrol and its derivative acetyl-resveratrol may inhibit in vitro 3D cell growth of certain subtypes of ovarian cancer, and growth restriction may be associated with the secretion of VEGF under the control of the NF-κB protein.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Otago, Christchurch, 2 Riccarton Avenue, Christchurch, 8011, New Zealand.
authors.forename: Alexandria B
authors.initials: AB
authors.lastname: Tino
authors.affiliation: Obstetrics and Gynaecology Department Christchurch Women's Hospital, Private Bag 4711, Christchurch, 8140, New Zealand. kenny.chitcholtan@otago.ac.nz.
authors.forename: Kenny
authors.identifier: http://orcid.org/0000-0002-9978-4786
authors.initials: K
authors.lastname: Chitcholtan
authors.affiliation: Department of Obstetrics and Gynaecology, University of Otago, Christchurch, 2 Riccarton Avenue, Christchurch, 8011, New Zealand.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Sykes
authors.affiliation: School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch, 8140, New Zealand.
authors.forename: Ashley
authors.initials: A
authors.lastname: Garrill
mesh_terms: D002449:Cell Aggregation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D018874:Spheroids, Cellular; D013267:Stilbenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D013267:Stilbenes; D042461:Vascular Endothelial Growth Factor A; D000077185:Resveratrol
keywords: Acetyl-resveratrol; Cell clusters; IL-8; NF-κB; Ovarian cancer; Resveratrol; VEGF