Suppression of ultraviolet B exposure-mediated activation of NF-kappaB in normal human keratinocytes by resveratrol.
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.
Adhami
Vaqar Mustafa
VM
Department of Dermatology, University of Wisconsin, Madison, WI 53706, USA. nahmad@wisc.edu
Afaq
Farrukh
F
Ahmad
Nihal
N
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000378:metabolism; D015151:Immunoblotting; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077185:Resveratrol; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors; D051996:Transcription Factor RelA; D014158:Transcription, Genetic / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays
D016588:Anticarcinogenic Agents; D020672:I-kappa B Proteins; D016328:NF-kappa B; D013267:Stilbenes; D051996:Transcription Factor RelA; D012264:Ribonucleotide Reductases; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; D000077185:Resveratrol