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.