title: Dose-dependent effect of resveratrol on bladder cancer cells: chemoprevention and oxidative stress.
abstract: BACKGROUND
  Over 6 million people die annually in the world because of cancer. Several groups are focused on studying cancer chemoprevention approaches. Resveratrol, a polyphenol, at high dosages, has been reported as antitumor and chemopreventive. However, it has a dose-dependent effect on cell death, even on some cancer cells.
  
  
  OBJECTIVE
  Our aim was to investigate this dose-dependent effect on human bladder carcinoma ECV304 cells during oxidative stress condition.
  
  
  METHODS
  For this purpose, ECV304 cells incubated with different Resveratrol concentrations were analyzed as for their metabolic rate, membrane permeability, DNA fragmentation, anti/proapoptotic protein levels and phosphatidylserine exposure after oxidative stress.
  
  
  RESULTS
  Resveratrol induced cell death at high concentrations (>20 μM), but not at low ones (0.1-20 μM). Pretreatment with 2.5 μM protected the cells from oxidative damage, whereas 50 μM intensified the cell death and significantly increased Bad/Bcl-2 ratio (proapoptotic/antiapoptotic proteins). Resveratrol was able to modulate NO and PGE(2) secretion and performed an anti-adhesion activity of neutrophils on PMA-activated ECV304 cells.
  
  
  CONCLUSIONS
  Resveratrol at high doses induces cell death of ECV304 cells whereas low doses induce protection. Modulation of Bcl-2 protein induced by Resveratrol could be mediating this effect. This information about the role of Resveratrol on cancer alerts us about its dose-dependent effects and could lead the design of future chemoprevention strategies.
authors.affiliation: Faculty of Pharmaceutical Sciences of Ribeirao Preto, Laboratory of Clinical Cytology, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Bianca
authors.initials: B
authors.lastname: Stocco
authors.forename: Karina
authors.initials: K
authors.lastname: Toledo
authors.forename: Mirian
authors.initials: M
authors.lastname: Salvador
authors.forename: Michele
authors.initials: M
authors.lastname: Paulo
authors.forename: Natália
authors.initials: N
authors.lastname: Koyama
authors.forename: Maria Regina
authors.initials: MR
authors.lastname: Torqueti Toloi
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009504:Neutrophils / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D013755:Tetradecanoylphorbol Acetate; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D013267:Stilbenes; D051025:bcl-Associated Death Protein; D009569:Nitric Oxide; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D000077185:Resveratrol