Two dietary polyphenols, fisetin and luteolin, reduce inflammation but augment DNA damage-induced toxicity in human RPE cells

J Nutr Biochem. 2017 Apr:42:37-42. doi: 10.1016/j.jnutbio.2016.12.014. Epub 2017 Jan 9.


Plant-derived polyphenols are known to possess anti-inflammatory and antioxidant effects. In recent years, several studies have investigated their potential benefits for treating chronic diseases associated with prolonged inflammation and excessive oxidative stress, such as age-related macular degeneration (AMD). Previously, two polyphenols, fisetin and luteolin, have been reported to increase the survival of retinal pigment epithelial (RPE) cells suffering from oxidative stress as well as decreasing inflammation but the benefits of polyphenol therapy seem to depend on the model system used. Our aim was to analyze the effects of fisetin and luteolin on inflammation and cellular viability in a model of nonoxidative DNA damage-induced cell death in human RPE (hRPE) cells. Pretreatment of ARPE-19 or primary hRPE cells with the polyphenols augmented etoposide-induced cell death as measured by the lactate dehydrogenase and 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. However, the treatment was able to reduce the release of two proinflammatory cytokines, IL-6 and IL-8, which were determined by enzyme-linked Immunosorbent assay. Analyses of caspase 3 activity, p53 acetylation and SIRT1 protein levels revealed the apoptotic nature of etoposide-evoked cell death and that fisetin and luteolin augmented the etoposide-induced acetylation of p53 and decreased SIRT1 levels. Taken together, our findings suggest that the cytoprotective effects of fisetin and luteolin depend on the stressor they need to combat, whereas their anti-inflammatory potential is sustained over a variety of model systems. Careful consideration of disease pathways will be necessary before fisetin or luteolin can be recommended as therapeutic agents for inflammatory diseases in general and specifically AMD.

Keywords: Age-related macular degeneration; DNA damage; Dietary polyphenols; Fisetin; Inflammation; Luteolin.

MeSH terms

  • Acetylation / drug effects
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Cell Death / drug effects
  • Cell Line
  • Cytokines / metabolism
  • DNA Damage / drug effects*
  • Dietary Supplements
  • Etoposide / adverse effects
  • Flavonoids / pharmacology*
  • Flavonols
  • Humans
  • Luteolin / pharmacology*
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigment Epithelium / pathology
  • Retinitis / drug therapy
  • Sirtuin 1 / metabolism
  • Tumor Suppressor Protein p53 / metabolism


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Flavonoids
  • Flavonols
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Etoposide
  • SIRT1 protein, human
  • Sirtuin 1
  • Luteolin
  • fisetin