Topical Treatment with Black Raspberry Extract Reduces Cutaneous UVB-Induced Carcinogenesis and Inflammation

被引:55
作者
Duncan, F. J. [1 ,3 ]
Martin, Jason R. [1 ,3 ]
Wulff, Brian C. [1 ]
Stoner, Gary D. [2 ]
Tober, Kathleen L. [1 ]
Oberyszyn, Tatiana M. [1 ]
Kusewitt, Donna F. [4 ]
Van Buskirk, Anne M. [3 ]
机构
[1] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA
[2] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA
[3] Ohio State Univ, Dept Surg, Columbus, OH 43210 USA
[4] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Div Sci Pk Res, Smithville, TX USA
关键词
INDUCED SKIN-CANCER; T-CELLS; ULTRAVIOLET-RADIATION; MEDIATED INFLAMMATION; COLON-CANCER; B RADIATION; MOUSE MODEL; INHIBITION; APOPTOSIS; INDUCTION;
D O I
10.1158/1940-6207.CAPR-08-0193
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
m Light in the UVB spectrum (280-320 nm) induces a number of changes in the epidermis and dermis of mice and humans, resulting in a robust inflammatory response. A standardized black raspberry extract (BRE) has been effective in reducing signaling pathways commonly initiated by inflammatory stimuli. In this study, we determined whether this extract could reduce cutaneous UVB-induced inflammation and carcinogenesis. In our carcinogenesis model, female SKH-1 hairless mice were exposed to one minimal erythemal dose of UVB thrice weekly on nonconsecutive days for 25 weeks. Immediately after each exposure, the mice were treated topically with either BRE dissolved in vehicle or with vehicle only. Beginning on week 19, mice treated with BRE had a significant reduction in tumor number and in average tumor size. This reduction correlated with a significant reduction in tumor-infiltrating CD3(+)foxp3(+) regulatory T-cells. In the acute model, mice were exposed to a single minimal erythemal dose of UVB and treated topically with BRE or with vehicle. At 48 hours post-UVB exposure, topical BRE treatment significantly reduced edema, p53 protein levels, oxidative DNA damage, and neutrophil activation. The ability of topical BRE to reduce acute UVB-induced inflammation and to decrease tumor development in a long-term model provides compelling evidence to explore the clinical efficacy of BRE in the prevention of human skin cancers.
引用
收藏
页码:665 / 672
页数:8
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