Effect of caffeine on UVB-induced carcinogenesis, apoptosis, and the elimination of UVB-induced patches of p53 mutant epidermal cells in SKH-1 mice.
Oral administration of green tea or caffeine to SKH-1 mice during UVB irradiation for several months inhibited the formation of skin cancer. Similar effects were observed when green tea or caffeine was given to tumor-free UVB-initiated mice with a high risk of developing skin tumors in the absence of further UVB irradiation (high risk mice). Mechanistic studies indicated that topical application of caffeine stimulated UVB-induced apoptosis as well as apoptosis in UVB-induced focal hyperplasia and tumors in tumor-bearing mice. Oral or topical administration of caffeine enhanced the removal of patches of epidermal cells with a mutant form of p53 protein that appeared early during the course of UVB-induced carcinogenesis, and oral administration of caffeine altered the profile of p53 mutations in the patches. In additional studies, topical application of caffeine was shown to have a sunscreen effect, and topical application of caffeine sodium benzoate was more active than caffeine as a sunscreen and for stimulating UVB-induced apoptosis. Caffeine sodium benzoate was also highly active in inhibiting carcinogenesis in UVB-pretreated high risk mice. Our studies indicate that caffeine and caffeine sodium benzoate may be useful as novel inhibitors of sunlight-induced skin cancer.
Conney
Allan H
AH
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA. aconney@rci.rutgers.edu
Kramata
Pavel
P
Lou
You-Rong
YR
Lu
Yao-Ping
YP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000528:radiation effects; D051379:Mice; D009381:Neoplasms, Radiation-Induced / Q000473:pathology*; D012878:Skin Neoplasms / Q000209:etiology* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014466:Ultraviolet Rays
D016159:Tumor Suppressor Protein p53; D002110:Caffeine