Oral caffeine during voluntary exercise markedly inhibits skin carcinogenesis and decreases inflammatory cytokines in UVB-treated mice.
Ultraviolet B (UVB)-pretreated SKH-1 mice were treated with water, caffeine (0.1 mg/ml), voluntary running wheel exercise (RW) or caffeine together with RW for 14 wk. Treatment of the mice with caffeine, RW, or caffeine plus RW decreased skin tumors per mouse by 27%, 35%, and 62%, respectively, and the tumor volume per mouse was decreased by 61%, 70%, and 85%, respectively. In mechanistic studies, mice were treated with water, caffeine, RW, or caffeine plus RW for 2 wk prior to a single irradiation with UVB. Caffeine plus RW increased RW activity by 22% when compared with RW alone. Caffeine ingestion was not significantly different between groups. Treatment of mice with caffeine plus RW for 2 wk decreased the weight of the parametrial fat pads and stimulated the formation of UVB-induced apoptosis to a greater extent than treatment with caffeine or RW alone. An antibody array revealed that caffeine plus RW administered to mice fed a high-fat diet and irradiated with UVB decreased the epidermal levels of lipopolysaccharide-induced CXC chemokine, soluble TNF alpha receptor-1, and macrophage inflammatory protein-1γ. Overall, caffeine during RW exerts a stronger effect than either treatment alone for decreasing tissue fat, increasing UVB-induced apoptosis, lowering the levels of cytokines associated with inflammation and for inhibiting UVB-induced carcinogenesis.
a Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers , The State University of New Jersey , Piscataway , New Jersey , USA.
Yourong
Y
Lou
Qingyun
Q
Peng
Tao
T
Li
Bonnie
B
Nolan
Jamie J
JJ
Bernard
George C
GC
Wagner
Yong
Y
Lin
Weichung Joe
WJ
Shih
Allan H
AH
Conney
Yaoping
Y
Lu
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002110:Caffeine / Q000008:administration & dosage*; D063646:Carcinogenesis / Q000187:drug effects*; D019742:Chemokines, CC / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat; D005260:Female; D007249:Inflammation / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000009:adverse effects; D051379:Mice; D018345:Mice, Knockout; D010805:Physical Conditioning, Animal; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
D019742:Chemokines, CC; D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002110:Caffeine