UVB-Pretreated High-Risk Mice Research Articles

Abstract 4286: Oral caffeine during voluntary exercise markedly inhibits skin carcinogenesis and decreases cytokines associated with inflammation in UVB-treated mice

Abstract In previous studies, we found that treatment of female SKH-1 mice with either oral administration of caffeine or voluntary running wheel exercise (RW) inhibited the formation of UVB-induced skin tumors. In the present study, we determined whether RW in combination with oral caffeine has a synergistic inhibitory effect on UVB-induced skin carcinogenesis. UVB-pretreated female high-risk SKH-1 mice (7-8 weeks of age, total 160 mice) have no tumors but they develop tumors in the absence of further UVB irradiation over the next several months. These high-risk mice (40 mice per group) were then treated with water (control), caffeine (0.1 mg/ml in drinking fluid), RW or caffeine together with RW for 14 weeks. Although there were no differences in body weight between the four groups during the course of the study, treatment with caffeine increased running wheel activity by 40% when compared with RW alone. Treatment of the mice with caffeine, RW or caffeine together with RW decreased skin tumors per mouse by 27, 35 and 62%, respectively, and the tumor volume per mouse was decreased by 61, 70 and 85%, respectively. In mechanistic studies, female SKH-1 mice were treated with water (control), caffeine (0.1 mg/ml), RW, or a combination of caffeine plus RW for 2 weeks. All mice were then exposed to a single dose of UVB (30 mJ/cm2) and sacrificed before (control) and at 0.1, 0.5, 1, 2, 4, 6, 10, 16, 24, and 48 h post UVB. The results showed that mice treated with oral caffeine for 2 weeks increased RW activity by 22% when compared with the mice treated with RW alone. Treatment of mice orally with caffeine, RW, or a combination of caffeine and RW for 2 weeks (a) decreased the weight of the parametrial fat pads by 30, 56 and 63%, respectively, (b) stimulated the formation of UVB-induced apoptotic sunburn cells in the epidermis by 21, 124 and 298% at 6 hours post-UVB, and stimulated the formation of UVB-induced caspase 3 (active form) positive cells in the epidermis by 30, 164 and 333%, respectively at 6 hours post-UVB. Combination treatment of the mice had a small but significant inhibitory effect on cell proliferation as measured by bromodeoxyuridine incorporation into DNA in the epidermis. Antibody array with 40 cytokines associated with inflammation revealed that oral caffeine together with RW administered to mice fed a high fat diet rich in omega-6 fatty acids for 2 weeks significantly decreased the UVB-induced increases in the levels of LIX, sTNF R1 and MIP-1α as well as several other cytokines associated with inflammation. Our results indicate that voluntary exercise in combination with oral caffeine exerts a stronger effect than either treatment alone for decreasing tissue fat, increasing UVB-induced apoptosis, lowering the levels of cytokines associated with inflammation and for inhibiting UVB-induced carcinogenesis in UVB-pretreated high-risk mice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4286. doi:1538-7445.AM2012-4286

Tumorigenic Effect of Some Commonly Used Moisturizing Creams when Applied Topically to UVB-Pretreated High-Risk Mice

Tumorigenic Effect of Some Commonly Used Moisturizing Creams when Applied Topically to UVB-Pretreated High-Risk Mice

Tumorigenic Effect of Some Commonly Used Moisturizing Creams when Applied Topically to UVB-Pretreated High-Risk Mice

Irradiation of SKH-1 mice with UVB (30 mJ cm(-2)) twice a week for 20 weeks resulted in mice with a high risk of developing skin tumors over the next several months in the absence of further irradiation with UVB (high-risk mice). Topical applications of 100 mg of Dermabase, Dermovan, Eucerin Original Moisturizing Cream (Eucerin), or Vanicream once a day, 5 days a week for 17 weeks to these high-risk mice increased significantly the rate of formation of tumors and the rate of increase in tumor size per mouse. Additional studies indicated that treatment of high-risk mice with Dermabase, Dermovan, Eucerin, or Vanicream for 17 weeks increased the total number of histologically characterized tumors by 69% (average of two experiments; P<0.0001 in each experiment), 95% (P<0.0001), 24% (P<0.01), and 58% (P<0.0001), respectively. Topical applications of a specially designed Custom Blend cream to high-risk mice was not tumorigenic. The results indicate that several commercially available moisturizing creams increase the rate of formation and number of tumors when applied topically to UVB-pretreated high-risk mice. Further studies are needed to determine the effects of topical applications of moisturizing creams on sunlight-induced skin cancer in humans.

Effect of Caffeine on UVB‐induced Carcinogenesis, Apoptosis, and the Elimination of UVB‐induced Patches of p53 Mutant Epidermal Cells in SKH‐1 Mice†

Oral administration of green tea or caffeine to SKH-1 mice during UVB irradiation for several months inhibited the formation of skin cancer. Similar effects were observed when green tea or caffeine was given to tumor-free UVB-initiated mice with a high risk of developing skin tumors in the absence of further UVB irradiation (high risk mice). Mechanistic studies indicated that topical application of caffeine stimulated UVB-induced apoptosis as well as apoptosis in UVB-induced focal hyperplasia and tumors in tumor-bearing mice. Oral or topical administration of caffeine enhanced the removal of patches of epidermal cells with a mutant form of p53 protein that appeared early during the course of UVB-induced carcinogenesis, and oral administration of caffeine altered the profile of p53 mutations in the patches. In additional studies, topical application of caffeine was shown to have a sunscreen effect, and topical application of caffeine sodium benzoate was more active than caffeine as a sunscreen and for stimulating UVB-induced apoptosis. Caffeine sodium benzoate was also highly active in inhibiting carcinogenesis in UVB-pretreated high risk mice. Our studies indicate that caffeine and caffeine sodium benzoate may be useful as novel inhibitors of sunlight-induced skin cancer.