title: Suppression of ultraviolet B exposure-mediated activation of NF-kappaB in normal human keratinocytes by resveratrol.
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.
authors.affiliation: Department of Dermatology, University of Wisconsin, Madison, WI 53706, USA. nahmad@wisc.edu
authors.forename: Vaqar Mustafa
authors.initials: VM
authors.lastname: Adhami
authors.forename: Farrukh
authors.initials: F
authors.lastname: Afaq
authors.forename: Nihal
authors.initials: N
authors.lastname: Ahmad
mesh_terms: 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
chemical_list: 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