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BIOLOGICAL SCIENCES / PHARMACOLOGY
Voluntary exercise together with oral caffeine markedly stimulates UVB light-induced apoptosis and decreases tissue fat in SKH-1 mice
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*Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Department of Neuroscience, and Department of Psychology, Rutgers, the State University of New Jersey, Piscataway, NJ 08854
Contributed by Allan H. Conney, June 21, 2007 (received for review April 17, 2007)
Treatment of SKH-1 mice orally with caffeine (0.1 mg/ml in the drinking water), voluntary running wheel exercise, or a combination of caffeine and exercise for 2 weeks (i) decreased the weight of the parametrial fat pads by 35, 62, and 77%, respectively; (ii) decreased the thickness of the dermal fat layer by 38, 42, and 68%, respectively; (iii) stimulated the formation of UVB-induced apoptotic sunburn cells in the epidermis by 96, 120, and 376%, respectively; and (iv) stimulated the formation of UVB-induced caspase 3 (active form)-positive cells in the epidermis by 92, 120, and 389%, respectively (average of two experiments). Oral administration of caffeine (0.4 mg/ml in the drinking water) in combination with voluntary exercise was less effective than administration of the low dose of caffeine in combination with exercise in stimulating UVB-induced apoptosis. Although orally administrated caffeine (0.1 mg/ml in the drinking water) or voluntary exercise for 2 weeks caused only a small nonsignificant stimulation of UVB-induced increase in the percentage of phospho-p53 (Ser-15)-positive cells in the epidermis (27 or 18%, respectively), the combination of the two treatments enhanced the UVB-induced increase in phospho-p53 (Ser-15)-positive cells by 99%. The plasma concentration of caffeine in mice ingesting caffeine (0.1–0.4 mg/ml drinking water) is similar to that in the plasma of most coffee drinkers (one to four cups per day). Our studies indicate a greater than additive stimulatory effect of combined voluntary exercise and oral administration of a low dose of caffeine on UVB-induced apoptosis.
methylxanthines | physical activity | programmed cell death | skin cancer | sunburn
The authors declare no conflict of interest.
¶ Lu, Y-P., Lou, Y-R., Peng, Q-Y., Xie, J-G., Nghiem, P., and Conney, A. H. (2007) Proc. Am. Assoc. Cancer Res. 48:821 (abstr.).
To whom correspondence should be addressed at: 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. E-mail: aconney{at}rci.rutgers.edu
© 2007 by The National Academy of Sciences of the USA
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