Stimulatory effect of topical application of caffeine on UVB-induced apoptosis in the epidermis of p53 and Bax knockout mice.
Shaved male or female p53(-/-) C57BL/6J mice and their wild-type littermates were irradiated once with UVB (60 mJ/cm(2)). The UVB-induced increase in apoptotic sunburn cells in p53(-/-) mice at 6-10 h after exposure to UVB was only 10-30% of that observed after treatment of p53(+/+) mice with UVB. Topical applications of caffeine immediately after UVB irradiation in female p53(+/+) or p53(-/-) mice enhanced the UVB-induced increase in apoptotic sunburn cells 6 h later by 127% and 563%, respectively. In another study, shaved female Bax(-/-) C57BL/6J mice and their wild-type littermates were irradiated once with UVB (60 mJ/cm(2)). The UVB-induced increase in apoptotic sunburn cells in Bax(-/-) mice at 6 h after exposure to UVB was only 14% of that observed after treatment of Bax(+/+) mice with UVB. Topical application of caffeine immediately after irradiation of Bax(+/+) or Bax(-/-) mice with UVB enhanced the UVB-induced increases in apoptotic sunburn cells at 6 h by 214% and 467%, respectively, and topical application of caffeine immediately after irradiation of Bax(+/+) or Bax(-/-) mice with UVB enhanced the UVB-induced increase in caspase 3 (active form) positive cells at 6 h by 253% and 750%, respectively. The results indicate that UVB-induced increases in apoptosis in the epidermis of wild-type mice are predominantly (but not entirely) by p53- and Bax-dependent pathways and that topical application of caffeine can enhance UVB-induced increases in apoptosis by p53- and Bax-independent pathways.
Lu
Yao-Ping
YP
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers-The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.
Lou
You-Rong
YR
Peng
Qing-Yun
QY
Xie
Jian-Guo
JG
Conney
Allan H
AH
D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002110:Caffeine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D013471:Sunburn / Q000209:etiology / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D002110:Caffeine