Stimulatory effect of topical application of caffeine on UVB-induced apoptosis in mouse skin.
In an earlier study, we showed that oral administration of green tea or caffeine to SKH-1 mice for 2 weeks prior to a single application of UVB enhanced UVB-induced increases in the number of p53-positive cells, p21(WAF1/CIP1)-positive cells, and apoptotic sunburn cells in the epidermis. In the present study, we found that topical application of caffeine, a major chemopreventive agent in tea, to the dorsal skin of SKH-1 mice immediately after irradiation with UVB (30 mJ/cm2) enhanced UVB-induced apoptosis as measured by the number of morphologically distinct epidermal apoptotic sunburn cells and the number of caspase 3-positive cells. Time course studies indicated that UVB-induced increases in apoptotic sunburn cells were correlated with elevated levels of caspase 3, a key protease that becomes activated during an early stage of apoptosis. Topical application of caffeine immediately after UVB enhanced UVB-induced increases in caspase 3 (active form)-immunoreactive-positive cells and in caspase 3 enzyme activity in the epidermis. Topical application of caffeine had only a small stimulatory effect on UVB-induced increases in the level of wild-type p53 protein and these changes were not related temporally to caffeine-induced increases in apoptotic cells. There was little or no effect of topical applications of caffeine on epidermal cell proliferation as determined by bromodeoxyuridine (BrdU) incorporation into DNA. Topical application of (-)-epigallocatechin gallate (EGCG) to the dorsal skin of mice immediately after irradiation with UVB had a small inhibitory effect on UVB-induced increases in BrdU-positive cells in the basal layer of the epidermis, but this treatment had no effect on UVB-induced increases in apoptotic sunburn cells. The results of this study indicate a proapoptotic effect of topical application of caffeine on UVB-irradiated mouse skin.
Lu
Yao-Ping
YP
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
Lou
You-Rong
YR
Li
Xiang-Hong
XH
Xie
Jian-Guo
JG
Lin
Yong
Y
Shih
Weichung Joe
WJ
Conney
Allan H
AH
D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D012867:Skin / Q000187:drug effects / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014466:Ultraviolet Rays
D016159:Tumor Suppressor Protein p53; D002110:Caffeine; D002392:Catechin; C045651:epigallocatechin gallate; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases