Oral administration of caffeine during voluntary exercise markedly decreases tissue fat and stimulates apoptosis and cyclin B1 in UVB-treated skin of hairless p53-knockout mice.
Treatment of p53(-/-) mice orally with caffeine, voluntary exercise or their combination for 2 weeks prior to a single irradiation with UVB (i) decreased the weight of the epididymal fat pads by 22, 40 and 56%, (ii) decreased the thickness of the dermal fat layer by 10, 26 and 42%, (iii) increased the number of apoptotic sunburn cells by 29, 100 and 489%, (iv) increased the number of caspase-3-positive cells by 33, 117 and 667% and (v) increased the number of mitotic cells with cyclin B1-positive staining by 40, 210 and 510%, respectively. Pearson's correlation coefficient indicated a statistically significant inverse relationship between the level of tissue fat and the number of mitotic cells with cyclin B1 in p53(-/-) mice but not in p53(+/+) littermates. Western blot analysis indicated that treatment of p53(-/-) mice with caffeine together with exercise increased the level of cyclin B1 significantly more than in p53(+/+) mice. p53(-/-) mice, but not p53(+/+) mice, treated with caffeine during exercise exhibited a dramatic decrease in the level of survivin. Our results suggest that voluntary exercise in combination with oral caffeine may exert a synergistic increase in UVB-induced apoptosis and that tissue fat may be a more important modulator of apoptosis and carcinogenesis in p53-deficient mice than in p53-normal mice. The stimulatory effects on apoptosis in p53(-/-) mice by the combination treatment might be associated with increased levels of cyclin B1 and decreased levels of survivin.
Lou
Yourong
Y
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Peng
Qingyun
Q
Nolan
Bonnie
B
Wagner
George C
GC
Lu
Yaoping
Y
D000273:Adipose Tissue / Q000187:drug effects*; D000284:Administration, Oral; D000818:Animals; D000918:Antibody Specificity; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D001835:Body Weight; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D056744:Cyclin B1 / Q000032:analysis* / Q000276:immunology; D004326:Drinking; D004435:Eating; D004822:Epididymis / Q000187:drug effects; D005260:Female; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000032:analysis; D010805:Physical Conditioning, Animal; D012097:Repressor Proteins; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014466:Ultraviolet Rays
C117749:Birc5 protein, mouse; C534700:Ccnb1 protein, mouse; D056744:Cyclin B1; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D012097:Repressor Proteins; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D002110:Caffeine