Resveratrol-sensitized UVA induced apoptosis in human keratinocytes through mitochondrial oxidative stress and pore opening

J Photochem Photobiol B. 2012 Aug 1;113:42-50. doi: 10.1016/j.jphotobiol.2012.04.013. Epub 2012 May 18.

Abstract

Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a polyphenol compound, is derived from natural products such as the skin of red grapes, blueberries and cranberries. Resveratrol not only exhibits antioxidant, cardioprotection, and anti-aging properties, but can also inhibit cancer cell growth and induce apoptosis. It has been shown that resveratrol inhibits the activation of Nf-κB and subsequently down regulates the expression of Nf-κB regulated genes such as interleukin-2 and Bcl-2, leading to cell cycle arrest and increased apoptosis in multiple myeloma cells. In the skin, resveratrol has been reported to sensitize keratinocytes to UVA induced apoptosis. However, the effect of resveratrol on opening of the mitochondrial permeability transition pore has not been previously examined. Our data show that UVA (14 J/cm(2)) along with resveratrol causes massive oxidative stress in mitochondria. As a consequence of oxidative stress, the mitochondrial membrane potential decreases which results in opening of the mitochondrial pores ultimately leading to apoptosis in human keratinocytes. These results may have clinical implications for development of future chemotherapeutic treatment for tumors of the skin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / radiation effects*
  • HEK293 Cells
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / radiation effects*
  • Mitochondria / drug effects
  • Mitochondria / radiation effects*
  • Mitochondrial Membrane Transport Proteins / drug effects
  • Mitochondrial Membrane Transport Proteins / radiation effects*
  • Mitochondrial Permeability Transition Pore
  • Oxidative Stress / drug effects
  • Oxidative Stress / radiation effects*
  • Resveratrol
  • Stilbenes / pharmacology*
  • Ultraviolet Rays*

Substances

  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Stilbenes
  • Resveratrol