Caffeine and caffeine sodium benzoate have a sunscreen effect, enhance UVB-induced apoptosis, and inhibit UVB-induced skin carcinogenesis in SKH-1 mice.
Topical application of caffeine sodium benzoate (caffeine-SB) immediately after UVB irradiation of SKH-1 mice enhanced UVB-induced apoptosis by a 2- to 3-fold greater extent than occurred after the topical application of an equimolar amount of caffeine. Although topical application of caffeine-SB or caffeine enhanced UVB-induced apoptosis, both substances were inactive on non-UVB-treated normal skin. Topical application of caffeine-SB or caffeine (each has UVB absorption properties) 0.5 h before irradiation with a high dose of UVB decreased UVB-induced thymine dimer formation and sunburn lesions (sunscreen effect). Caffeine-SB was more active than an equimolar amount of caffeine in exerting a sunscreen effect. In additional studies, caffeine-SB strongly inhibited the formation of tumors in UVB-pretreated 'high-risk mice' and in tumor-bearing mice, and the growth of UVB-induced tumors was also inhibited. Caffeine-SB and caffeine are the first examples of compounds that have both a sunscreen effect and enhance UVB-induced apoptosis. Our studies suggest that caffeine-SB and caffeine may be good agents for inhibiting the formation of sunlight-induced skin cancer.
Lu
Yao-Ping
YP
William M. and Myrle W. Garbe Professor of Cancer and Leukemia Research, Ernest Mario School of Pharmacy, Rutgers, NJ, USA.
Lou
You-Rong
YR
Xie
Jian-Guo
JG
Peng
Qing-Yun
QY
Zhou
Sherry
S
Lin
Yong
Y
Shih
Weichung Joe
WJ
Conney
Allan H
AH
D000287:Administration, Topical; D000818:Animals; D016587:Antimutagenic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D001565:Benzoates / Q000627:therapeutic use*; D002110:Caffeine / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects; D000697:Central Nervous System Stimulants / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009381:Neoplasms, Radiation-Induced / Q000188:drug therapy* / Q000473:pathology; D011740:Pyrimidine Dimers; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013471:Sunburn / Q000209:etiology / Q000473:pathology; D013473:Sunscreening Agents / Q000627:therapeutic use*; D014466:Ultraviolet Rays
D016587:Antimutagenic Agents; D001565:Benzoates; D000697:Central Nervous System Stimulants; D004338:Drug Combinations; D011740:Pyrimidine Dimers; D013473:Sunscreening Agents; D002110:Caffeine; C025741:caffeine, sodium benzoate drug combination