Epigallocatechin-3-gallate inhibits photocarcinogenesis through inhibition of anglogenic factors and activation of CD8+ T cells in tumors (Retracted article. See vol. 94, pg. 618, 2018)
Epigallocatechin-3-gallate inhibits photocarcinogenesis through inhibition of anglogenic factors and activation of CD8+ T cells in tumors (Retracted article. See vol. 94, pg. 618, 2018)
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DOI：
10.1562/2005-04-11-ra-487
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发表时间：
2005-09-01
影响因子：
3.3
通讯作者：
Katiyar, SK
中科院分区：
文献类型：
--
作者：
Mantena, SK;Roy, AM;Katiyar, SK
使用植物补充剂来保护皮肤免受太阳紫外线辐射的不利影响，包括光致癌，已经引起了相当大的兴趣。我们和其他人已经证明，局部应用绿茶中的(-)-表没食子儿茶素没食子酸酯(EGCG)可以防止小鼠发生光癌；然而，在体内肿瘤模型中，EGCG的化学预防机制尚不清楚。在这项研究中，利用紫外线-B诱导的皮肤肿瘤和EGCG治疗前后的皮肤肿瘤(约1 mg/cm(2))和年龄匹配的SKH-1无毛小鼠皮肤活检组织，以确定EGCG预防皮肤癌的潜在分子靶点。用免疫染色、Western blotting和明胶溶解酶谱分析这些活检组织中血管生成和抗肿瘤免疫反应的各种生物标志物。我们报道，与未经EGCG治疗的肿瘤相比，在紫外线诱导的肿瘤中局部应用EGCG可抑制在肿瘤生长和转移中起关键作用的基质金属蛋白酶(MMP2)和MMP9的蛋白表达和活性。相反，抑制基质金属蛋白酶活性的基质金属蛋白酶组织抑制因子-1(TIMP-1)在肿瘤中增加。在肿瘤血管系统方面，EGCG降低了血管内皮细胞的细胞表面标志CD31的表达，抑制了肿瘤中血管内皮生长因子的表达，而血管内皮生长因子是肿瘤血管生成所必需的。EGCG对UV-B诱导的肿瘤增殖细胞核抗原也有抑制作用。此外，与非EGCG治疗的肿瘤相比，EGCG治疗的肿瘤中检测到更多的细胞毒性T淋巴细胞(CD8(+)T细胞)。综上所述，这些体内肿瘤数据表明，EGCG对小鼠光癌的抑制与抑制血管生成因子和诱导抗肿瘤免疫反应有关。
There has been considerable interest in the use of botanical supplements to protect skin from the adverse effects of solar UV radiation, including photocarcinogenesis. We and others have shown that topical application of (-)-epigallocatechin-3-gallate (EGCG) from green tea prevents photocarcinogenesis in mice; however, the chemopreventive mechanism of EGCG in an in vivo tumor model is not clearly understood. In this study, UV-B-induced skin tumors with and without treatment of EGCG (approximate to 1 mg/cm(2)) and age-matched skin biopsies from SKH-1 hairless mice were used to identify potential molecular targets of skin cancer prevention by EGCG. These biopsies were analyzed for various biomarkers of angiogenesis and antitumor immune response using immunostaining, Western blotting and gelatinolytic zymography. We report that compared to non-EGCG-treated tumors, topical application of EGCG in UV-induced tumors resulted in inhibition of protein expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9, which play crucial roles in tumor growth and metastasis. In contrast, tissue inhibitor of MMP-1 (TIMP-1), which inhibits MMP activity, was increased in tumors. With respect to the tumor vasculature, EGCG decreased the expression of CD31, a cell surface marker of vascular endothelial cells, and inhibited the expression of vascular endothelial growth factor in tumors, which are essential for angiogenesis. EGCG inhibited proliferating cell nuclear antigen in UV-B-induced tumors as well. Additionally, higher numbers of cytotoxic T lymphocytes (CD8(+) T cells) were detected in EGCG-treated tumors compared with non-EGCG-treated tumors. Together, these in vivo tumor data suggested that inhibition of photocarcinogenesis in mice by EGCG is associated with inhibition of angiogenic factors and induction of antitumor immune reactivity.