Journal Article

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

Yourong Lou, Qingyun Peng, Bonnie Nolan, George C. Wagner and Yaoping Lu

in Carcinogenesis

Volume 31, issue 4, pages 671-678
Published in print April 2010 | ISSN: 0143-3334
Published online November 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp288
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

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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.

Journal Article.  6582 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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