Suppression of ultraviolet B exposure-mediated activation of NF-kappaB in normal human keratinocytes by resveratrol

Neoplasia. Jan-Feb 2003;5(1):74-82. doi: 10.1016/s1476-5586(03)80019-2.

Abstract

Chemoprevention by naturally occurring agents is a newer dimension in the management of neoplasia, including skin cancer. Solar ultraviolet (UV) radiation is the major cause of skin cancer. We recently demonstrated that resveratrol (3,5,4'-trihydroxystilbene), a polyphenolic antioxidant found in grapes and red wine, imparts protection from UVB-mediated cutaneous damages in SKH-1 hairless mice. The mechanism of action of resveratrol is not clearly understood. Here, we investigated the involvement of nuclear factor kappa B (NF-kappaB), which is known to play a critical role in skin biology and the development of skin cancer, as the mechanism of chemoprevention of UV damage by resveratrol. In the normal human epidermal keratinocytes, resveratrol blocked UVB-mediated (40 mJ/cm(2)) activation of NF-kappaB in a dose-dependent (5, 10, and 25 micro M resveratrol for 24 hours) as well as time-dependent (5 micro M resveratrol for 12, 24, and 48 hours) fashion. Resveratrol treatment of keratinocytes also inhibited UVB-mediated 1) phosphorylation and degradation of IkappaBalpha, and 2) activation of IKKalpha. We suggest that NF-kappaB pathway plays a critical role in the chemopreventive effects of resveratrol against the adverse effects of UV radiation including photocarcinogenesis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anticarcinogenic Agents / pharmacology*
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Cytoplasm / metabolism
  • Dose-Response Relationship, Drug
  • Electrophoretic Mobility Shift Assay
  • Humans
  • I-kappa B Kinase
  • I-kappa B Proteins / metabolism
  • Immunoblotting
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Keratinocytes / radiation effects*
  • NF-kappa B / metabolism*
  • Phosphorylation / drug effects
  • Phosphorylation / radiation effects
  • Protein-Serine-Threonine Kinases / metabolism
  • Resveratrol
  • Ribonucleotide Reductases / antagonists & inhibitors
  • Stilbenes / pharmacology*
  • Time Factors
  • Transcription Factor RelA
  • Transcription, Genetic / drug effects*
  • Transcription, Genetic / radiation effects
  • Ultraviolet Rays*

Substances

  • Anticarcinogenic Agents
  • I-kappa B Proteins
  • NF-kappa B
  • Stilbenes
  • Transcription Factor RelA
  • Ribonucleotide Reductases
  • Protein-Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • Resveratrol