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
相关论文
共 56 条
[1]   Chemoprevention of photocarcinogenesis by selected dietary botanicals [J].
Baliga, MS ;
Katiyar, SK .
PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES, 2006, 5 (02) :243-253
[2]   Polydeoxyribonucleotide promotes cyclobutane pyrimidine dimer repair in UVB-exposed dermal fibroblasts [J].
Belletti, Silvana ;
Uggeri, Jacopo ;
Gatti, Rita ;
Govoni, Paolo ;
Guizzardi, Stefano .
PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE, 2007, 23 (06) :242-249
[3]   DNA lesions induced by UV A1 and B radiation in human cells:: Comparative analyses in the overall genome and in the p53 tumor suppressor gene [J].
Besaratinia, A ;
Synold, TW ;
Chen, HH ;
Chang, C ;
Xi, BX ;
Riggs, AD ;
Pfeifer, GP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (29) :10058-10063
[4]   The role of H2O2 as a mediator of UVB-induced apoptosis in keratinocytes [J].
Chang, H ;
Oehrl, W ;
Elsner, P ;
Thiele, JJ .
FREE RADICAL RESEARCH, 2003, 37 (06) :655-663
[5]   Chemopreventive properties of black raspberries in N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis:: Down-regulation of cyclooxygenase-2, inducible nitric oxide synthase, and c-Jun [J].
Chen, T ;
Hwang, HJ ;
Rose, ME ;
Nines, RG ;
Stoner, GD .
CANCER RESEARCH, 2006, 66 (05) :2853-2859
[6]   1,25-Dihydroxyvitamin D3 and analogues protect primary human keratinocytes against UVB-induced DNA damage [J].
De Haes, P ;
Garmyn, M ;
Verstuyf, A ;
De Clercq, P ;
Vandewalle, M ;
Degreef, H ;
Vantieghem, K ;
Bouillon, R ;
Segaert, S .
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 2005, 78 (02) :141-148
[7]   Clinically relevant immunosuppressants influence UVB-induced tumor size through effects on inflammation and angiogenesis [J].
Duncan, F. J. ;
Wulff, Brian C. ;
Tober, Kathleen L. ;
Ferketich, Amy K. ;
Martin, Jason ;
Thomas-Ahner, Jennifer M. ;
Allen, Stephanie D. ;
Kusewitt, Donna F. ;
Oberyszyn, Tatiana M. ;
VanBuskirk, Anne M. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2007, 7 (12) :2693-2703
[8]  
Eberlein-König B, 1998, BRIT J DERMATOL, V139, P415
[9]   Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemic cells by induction of oxidative stress [J].
Feng, Rentian ;
Ni, Hong-Min ;
Wang, Shiow Y. ;
Tourkova, Irina L. ;
Shurin, Michael R. ;
Harada, Hisashi ;
Yin, Xiao-Ming .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (18) :13468-13476
[10]   Induction of apoptosis in two human leukemia cell lines as well as differentiation in human promyelocytic cells by cyanidin-3-O-β-glucopyranoside [J].
Fimognari, C ;
Berti, F ;
Nüsse, B ;
Cantelli-Forti, G ;
Hrelia, P .
BIOCHEMICAL PHARMACOLOGY, 2004, 67 (11) :2047-2056