Dietary feeding of Silibinin prevents early biomarkers of UVB radiation-induced carcinogenesis in SKH-1 hairless mouse epidermis
Dietary feeding of Silibinin prevents early biomarkers of UVB radiation-induced carcinogenesis in SKH-1 hairless mouse epidermis
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DOI：
10.1158/1055-9965.epi-04-0664
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发表时间：
2005-05-01
影响因子：
3.8
通讯作者：
Agarwal, R
中科院分区：
文献类型：
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作者：
Gu, M;Dhanalakshmi, S;Agarwal, R
太阳辐射是非黑色素瘤皮肤癌（NMSC）发展的致病因素。平流层臭氧层的消耗导致环境紫外线辐射负荷的增加，预计这将进一步提高包括美国在内的世界许多温带地区的皮肤癌发病率，这表明通过生物标志物功效研究的皮肤癌化学预防方法或反之亦然是非常必要的。基于我们最近的研究报告了水飞蓟宾对抗光致癌作用的强大功效，我们在此评估了其饮食喂养对UVB诱导的NMSC相关生物标志物的保护作用，为早期水飞蓟宾在皮肤癌预防中的功效提供了机制原理。在以180 mJ/cm（2）剂量的UVB单次照射之前，以1%剂量（w/w）的水飞蓟宾饮食喂养SKH-1无毛小鼠2周，（P < 0.001）UVB诱导的胸腺嘧啶二聚体阳性细胞和增殖细胞核抗原减少，末端脱氧核苷酸转移酶介导的dUTP缺口末端标记，表皮细胞凋亡，p53和p21/cip 1阳性细胞数增加（P < 0.001）。这些研究结果表明，饮食喂养水飞蓟宾提供了强大的保护，防止UVB诱导的皮肤表皮损伤（a）防止DNA损伤或增强修复，（B）减少UVB诱导的过度增殖反应，（c）抑制UVB引起的细胞凋亡和晒伤细胞的形成，可能通过水飞蓟宾引起的上调p53和p21/cip 1作为主要的UVB损伤控制传感器。
Solar radiation is the causal etiologic factor in the development of nonmelanoma skin cancer (NMSC). Depletion of the stratospheric ozone layer leads to an increase in ambient UV radiation loads, which are expected to further raise skin cancer incidence in many temperate parts of the world, including the United States, suggesting that skin cancer chemopreventive approaches via biomarker efficacy studies or vice versa are highly warranted. Based on our recent study reporting strong efficacy of silibinin against photocarcinogenesis, we assessed here the protective effects of its dietary feeding on UVB-induced biomarkers involved in NMSC providing a mechanistic rationale for an early-on silibinin efficacy in skin cancer prevention. Dietary feeding of silibinin at 1% dose (w/w) to SKH-1 hairless mice for 2 weeks before a single UVB irradiation at 180 mJ/cm(2) dose resulted in a strong and significant (P < 0.001) decrease in UVB-induced thymine dimer-positive cells and proliferating cell nuclear antigen, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and apoptotic sunburn cells together with an increase (P < 0.001) in p53 and p21/cip1-positive cell population in epidermis. These findings suggest that dietary feeding of silibinin affords strong protection against UVB-induced damages in skin epidermis by (a) either preventing DNA damage or enhancing repair, (b) reducing UVB-induced hyperproliferative response, and (c) inhibiting UVB-caused apoptosis and sunburn cell formation, possibly via silibinin-caused up-regulation of p53 and p21/cip1 as major UVB-damage control sensors.