Inhibition of UVB-induced skin tumor development by drinking green tea polyphenols is mediated through DNA repair and subsequent inhibition of inflammation.
Consumption of green tea polyphenols (GTPs) in drinking water prevents photocarcinogenesis in mice; however, the molecular mechanisms underlying this effect have not been fully elucidated. Using IL-12p40 knockout (KO) mice and their wild-type counterparts and an established photocarcinogenesis protocol, we found that although administration of GTPs (0.2%, w/v) in drinking water significantly reduced UVB-induced tumor development in wild-type mice, this treatment had a nonsignificant effect in IL-12-KO mice. GTPs resulted in reduction in the levels of markers of inflammation (cyclooxygenase-2, prostaglandin E(2), proliferating cell nuclear antigen, and cyclin D1) and proinflammatory cytokines (tumor necrosis factor-alpha, IL-6, and IL-1beta) in chronically UVB-exposed skin and skin tumors of wild-type mice but less effective in IL-12p40-KO mice. UVB-induced DNA damage (cyclobutane pyrimidine dimers) was resolved rapidly in GTPs-treated wild-type mice than untreated wild-type mice and this resolution followed the same time course as the GTPs-induced reduction in the levels of inflammatory responses. This effect of GTPs was less pronounced in IL-12-KO mice. The above results were confirmed by treatment of IL-12-KO mice with murine recombinant IL-12 and treatment of wild-type mice with neutralizing anti-IL-12 antibody. To our knowledge, it is previously unreported that prevention of photocarcinogenesis by GTPs is mediated through IL-12-dependent DNA repair and a subsequent reduction in skin inflammation.
Meeran
Syed M
SM
Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Akhtar
Suhail
S
Katiyar
Santosh K
SK
D000284:Administration, Oral; D000818:Animals; D001628:Beverages; D019938:Cyclin D1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology* / Q000528:radiation effects; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D010636:Phenols / Q000008:administration & dosage / Q000627:therapeutic use*; D010936:Plant Extracts / Q000008:administration & dosage / Q000627:therapeutic use; D059808:Polyphenols; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012878:Skin Neoplasms / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D016207:Cytokines; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D018809:Proliferating Cell Nuclear Antigen; D019938:Cyclin D1; D018664:Interleukin-12; D051546:Cyclooxygenase 2; D015232:Dinoprostone