(-)-Epigallocatechin-3-gallate prevents photocarcinogenesis in mice through interleukin-12-dependent DNA repair.
We have shown previously that topical application of (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, prevents photocarcinogenesis in mice. EGCG prevents UVB-induced immunosuppression by inducing interleukin-12 (IL-12). As immunosuppression is a risk factor for photocarcinogenesis, we investigated the possibility that EGCG also prevents UVB-induced photocarcinogenesis through an IL-12-dependent DNA repair mechanism. To investigate this possibility, we determined the effects of EGCG on photocarcinogenesis in IL-12 knockout (KO) mice using the formation of cyclobutane pyrimidine dimers (CPD) as an indicator of the extent of UVB-induced DNA damage. Topical application of EGCG (1 mg/cm(2) skin) prevented photocarcinogenesis in wild-type (C3H/HeN) mice in terms of tumor incidence and tumor multiplicity but did not prevent photocarcinogenesis in IL-12 KO mice. UVB-induced DNA damage, as determined by the formation of CPDs and the number of sunburn cells, was resolved more rapidly in the skin of wild-type mice treated with EGCG than untreated control mice. In contrast, the extent of UVB-induced DNA damage and the numbers of sunburn cells were not significantly different in the EGCG-treated IL-12 KO mice and untreated control mice. In addition, treatment of XPA-proficient human fibroblast cells with EGCG promoted repair of UVB-induced CPDs in a dose-dependent manner but not in an XPA-deficient cells, indicating that the nucleotide excision repair mechanism is involved in EGCG-mediated DNA repair. Taken together, these results indicate for the first time that EGCG can prevent photocarcinogenesis through an EGCG-induced IL-12-dependent DNA repair mechanism.
Meeran
Syed M
SM
Department of Dermatology, University of Alabama at Birmingham and Birmingham VA Medical Center, Birmingham, Alabama 35294, USA.
Mantena
Sudheer K
SK
Elmets
Craig A
CA
Katiyar
Santosh K
SK
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004260:DNA Repair; D005260:Female; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D014466:Ultraviolet Rays; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics / Q000378:metabolism
D016588:Anticarcinogenic Agents; D011994:Recombinant Proteins; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse; D018664:Interleukin-12; D002392:Catechin; C045651:epigallocatechin gallate