Selenium for the prevention of cutaneous melanoma.

Selenium for the prevention of cutaneous melanoma.
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DOI:
10.3390/nu5030725
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发表时间:
2013-03-07
期刊:
影响因子:
5.9
通讯作者:
Leachman SA
Leachman SA
中科院分区:
医学2区
文献类型:
--
作者:
Cassidy PB;Fain HD;Cassidy JP Jr;Tran SM;Moos PJ;Boucher KM;Gerads R;Florell SR;Grossman D;Leachman SA

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硒(Se)补充剂在癌症预防中的作用是有争议的;效果通常取决于受试者的营养状况和提供Se的化学形式。我们使用了体外和体内模型相结合,研究两个独特的治疗窗口干预皮肤黑色素瘤的过程中,并检查两种不同的化学形式的硒预防和治疗黑色素瘤的效用。我们研究了硒在体外对紫外线诱导的黑素细胞氧化应激,黑色素瘤细胞凋亡和细胞周期进程的影响。在体内,我们使用的HGF转基因小鼠模型的紫外线诱导的黑色素瘤,以证明局部治疗与l-硒代蛋氨酸的结果在一个显着延迟的时间所需的紫外线诱导的黑色素瘤的发展,但也增加了这些肿瘤的生长速度,一旦他们出现。在第二个小鼠模型中,我们发现口服高剂量的甲基亚硒酸显著降低了人黑素瘤异种移植物的大小。我们的研究结果表明,皮肤中硒水平的适度升高可能会加速早期肿瘤的生长。此外,以非常高的剂量施用的某些硒化合物可用于治疗完全恶性肿瘤或预防复发。
The role of selenium (Se) supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence.
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