Abstract #928: Stimulatory effects of voluntary running wheel exercise together with oral administration of a low dose of caffeine on UVB-induced changes in apoptosis and cyclin B1 in the epidermis of hairless p53 knockout mice

Abstract

Our previous studies showed that voluntary running wheel exercise together with oral administration of caffeine may have a greater than additive effect in decreasing tissue fat and stimulating UVB-induced apoptosis in the epidermis of SKH-1 mice. Mechanistic studies indicated that caffeine administration inhibited the UVB-induced increase in p53-independent, ATR-mediated phosphorylation of Chk1 and prematurely increased the number of cyclin B1-containing cells that undergo lethal mitosis, and the stimulatory effect of voluntary exercise on apoptosis was also by a p53-independent pathway. In the present study, we explored whether voluntary running wheel exercise in combination with oral administration of a low dose of caffeine has a greater than additive effect on UVB-induced changes in apoptosis and cyclin B1 in the epidermis of p53 knockout mice. %9Treatment of male congenic hairless p53 homozygous knockout mice orally with 0.1 mg/ml of caffeine in the drinking water (a concentration expected to yield a plasma caffeine concentration similar to that observed in people drinking only one or two cups of coffee per day), voluntary running wheel exercise or their combination for 2 weeks prior to a single irradiation of 30 mJ/cm2 of UVB (a) decreased the weight of the epididymal fat pads by 13, 31 and 56%, respectively, (b) decreased the thickness of the dermal fat layer by 10, 26 and 42%, respectively, (c) stimulated the UVB-induced apoptosis (sunburn cells) in the epidermis at 6 hr post-UVB by 29, 100 and 489%, respectively, (d) increased the percentage of immunoreactive caspase 3 (active form) positive cells by 33, 117 and 667%, respectively, and (e) increased the percentage of mitotic cells with cyclin B1 by 40, 210 and 510%, respectively. Western blot analysis indicated that male congenic hairless p53 homozygous knockout mice or p53 heterozygous knockout mice treated orally with caffeine in combination with voluntary exercise for 2 weeks markedly increased the UVB-induced increase in the level of cyclin B1 at 6 hr post-UVB when compared with measurements after UVB, caffeine or exercise alone. The increased level of cyclin B1 in the epidermis of p53 homozygous knockout mice at 6 hr post-UVB was significantly higher than that in their p53 wild-type littermates. The addition of a low dose of caffeine treatment to the voluntary exercise regimen in p53 homozygous knockout mice stimulated food consumption by 20%, fluid consumption by 39%, and running wheel activity by 13%, but there was no changes in body weight. These results suggest that a greater than additive effect of combined voluntary exercise and oral administration of a low dose of caffeine on UVB-induced apoptosis and cyclin B1 was also observed in the skin of p53 deficient mice (Supported by NIH Grant RO1 CA128997 and RO1 CA114442).

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 928.