Hydroxytyrosol, a natural antioxidant from olive oil, prevents protein damage induced by long-wave ultraviolet radiation in melanoma cells

Free Radic Biol Med. 2005 Apr 1;38(7):908-19. doi: 10.1016/j.freeradbiomed.2004.12.015.


Previous studies showed that long-wave ultraviolet (UVA) radiation induces severe skin damage through the generation of reactive oxygen species and the depletion of endogenous antioxidant systems. Recent results from our laboratory indicate a dramatic increase of both lipid peroxidation products (TBARS) and abnormal L-isoaspartyl residues, marker of protein damage, in UVA-irradiated human melanoma cells. In this study, the effects of hydroxytyrosol (DOPET), the major antioxidant compound present in olive oil, on UVA-induced cell damages, have been investigated, using a human melanoma cell line (M14) as a model system. In UVA-irradiated M14 cells, a protective effect of DOPET in preventing the uprise of typical markers of oxidative stress, such as TBARS and 2'7'-dichlorofluorescein (DCF) fluorescence intensity, was observed. In addition, DOPET prevents the increase of altered L-isoAsp residues induced by UVA irradiation. These protective effects are dose dependent, reaching the maximum at 400 microM DOPET. At higher concentrations, DOPET causes an arrest of M14 cell proliferation and acts as a proapoptotic stimulus by activating caspase-3 activity. In the investigated model system, DOPET is quantitatively converted into its methylated derivative, endowed with a radical scavenging ability comparable to that of its parent compound. These findings are in line with the hypothesis that the oxidative stress plays a major role in mediating the UVA-induced protein damage. Results suggest that DOPET may exerts differential effects on melanoma cells according to the dose employed and this must always be taken into account when olive oil-derived large consumer products, including cosmetics and functional foods, are employed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Apoptosis
  • Humans
  • Isoaspartic Acid / analysis
  • Lipid Peroxidation / drug effects
  • Melanoma / metabolism*
  • Methylation / drug effects
  • Olive Oil
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / metabolism
  • Phenylethyl Alcohol / pharmacology
  • Plant Oils / chemistry
  • Proteins / chemistry
  • Proteins / metabolism
  • Proteins / radiation effects*
  • Reactive Oxygen Species / metabolism
  • Thiobarbituric Acid Reactive Substances / analysis
  • Tumor Cells, Cultured
  • Ultraviolet Rays*


  • Antioxidants
  • Isoaspartic Acid
  • Olive Oil
  • Plant Oils
  • Proteins
  • Reactive Oxygen Species
  • Thiobarbituric Acid Reactive Substances
  • 3,4-dihydroxyphenylethanol
  • Phenylethyl Alcohol