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Carcinogenesis. 2010 Apr;31(4):671-8. doi: 10.1093/carcin/bgp288. Epub 2009 Nov 19.

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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1
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.

Abstract

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.

PMID:
19926639
PMCID:
PMC2847084
DOI:
10.1093/carcin/bgp288
[Indexed for MEDLINE]
Free PMC Article
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