Topical treatment with black raspberry extract reduces cutaneous UVB-induced carcinogenesis and inflammation.

Topical treatment with black raspberry extract reduces cutaneous UVB-induced carcinogenesis and inflammation.
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DOI:
10.1158/1940-6207.capr-08-0193
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发表时间:
2009-07
期刊:
Cancer prevention research (Philadelphia, Pa.)
影响因子:
--
通讯作者:
Van Buskirk AM
Van Buskirk AM
中科院分区:
其他
文献类型:
--
作者:
Duncan FJ;Martin JR;Wulff BC;Stoner GD;Tober KL;Oberyszyn TM;Kusewitt DF;Van Buskirk AM

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UVB 光谱(280-320 nm)中的光会引起小鼠和人类的表皮和真皮发生许多变化,从而产生强烈的炎症反应。标准化黑树莓提取物 (BRE) 可有效减少通常由炎症刺激引发的信号通路。在这项研究中,我们确定了这种提取物是否可以减少 UVB 引起的皮肤炎症和致癌作用。在我们的致癌模型中,雌性 SKH-1 无毛小鼠每周三次接触一次最小红斑剂量的 UVB,不连续几天,持续 25 周。每次暴露后,立即用溶解在媒介物中的 BRE 或仅用媒介物局部治疗小鼠。从第 19 周开始,接受 BRE 治疗的小鼠肿瘤数量和平均肿瘤大小显着减少。这种减少与肿瘤浸润 CD3+foxp3+ 调节性 T 细胞的显着减少相关。在急性模型中,小鼠接受单次最小红斑剂量的 UVB 照射,并用 BRE 或载体进行局部治疗。 UVB 照射后 48 小时,局部 BRE 治疗显着减少水肿、p53 蛋白水平、氧化 DNA 损伤和中性粒细胞活化。在长期模型中,局部 BRE 能够减少 UVB 引起的急性炎症并减少肿瘤发展,这为探索 BRE 在预防人类皮肤癌方面的临床功效提供了令人信服的证据。
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.