Polyphenols in brewed green tea inhibit prostate tumor xenograft growth by localizing to the tumor and decreasing oxidative stress and angiogenesis.
Polyphenols in brewed green tea inhibit prostate tumor xenograft growth by localizing to the tumor and decreasing oxidative stress and angiogenesis.
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DOI：
10.1016/j.jnutbio.2011.10.007
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Heber D
中科院分区：
文献类型：
--
作者：
Henning SM;Wang P;Said J;Magyar C;Castor B;Doan N;Tosity C;Moro A;Gao K;Li L;Heber D
多种动物模型已证明，口服绿茶（GT）提取物和饮用水可以抑制肿瘤生长，但冲泡的GT对促进肿瘤生长的因素（包括DNA和蛋白质的氧化损伤、血管生成和DNA甲基化）的影响尚未在动物模型中进行测试。为了探索这些潜在机制，研究人员用酿造的GT代替饮用水给带有雄激素依赖性人LAPC4前列腺癌细胞皮下异种移植物的雄性严重联合免疫缺陷（SCID）小鼠。食用 GT 的小鼠肿瘤体积显着减小，且肿瘤大小与肿瘤组织中 GT 多酚 (GTP) 含量显着相关。缺氧诱导因子1-α和血管内皮生长因子蛋白表达显着减少。分别通过 8-羟基脱氧鸟苷/脱氧鸟苷比率和蛋白质羰基测定确定，GT 消耗显着减少了肿瘤组织中的氧化 DNA 和蛋白质损伤。已知甲基化会抑制谷胱甘肽 S-转移酶 pi (GSTp1) 等抗氧化酶，从而允许活性氧促进肿瘤生长。 GT 显着抑制肿瘤 5-胞嘧啶 DNA 甲基转移酶 1 (DNMT1) mRNA 和蛋白表达，这可能有助于通过抗氧化酶的重新激活抑制肿瘤生长。这项研究通过证明 GTP 的组织定位与肿瘤生长抑制的相关性，加深了我们对动物模型中酿造 GT 抑制肿瘤生长的理解。我们的结果表明，肿瘤生长的抑制是由于 GTP 介导的 SCID 小鼠 LAPC4 异种移植前列腺肿瘤氧化应激和血管生成的抑制。
It has been demonstrated in various animal models that the oral administration of green tea (GT) extracts in drinking water can inhibit tumor growth, but the effects of brewed GT on factors promoting tumor growth, including oxidant damage of DNA and protein, angiogenesis, and DNA methylation, have not been tested in an animal model. To explore these potential mechanisms, brewed GT was administered instead of drinking water to male severe combined immunodeficiency (SCID) mice with androgen-dependent human LAPC4 prostate cancer cell subcutaneous xenografts. Tumor volume was decreased significantly in mice consuming GT, and tumor size was significantly correlated with GT polyphenol (GTP) content in tumor tissue. There was a significant reduction in hypoxia-inducible factor 1-alpha and vascular endothelial growth factor protein expression. GT consumption significantly reduced oxidative DNA and protein damage in tumor tissue as determined by 8-hydroxydeoxyguanosine/deoxyguanosine ratio and protein carbonyl assay, respectively. Methylation is known to inhibit antioxidative enzymes such as glutathione S-transferase pi (GSTp1) to permit reactive oxygen species promotion of tumor growth. GT inhibited tumor 5-cytosine DNA methyltransferase 1 (DNMT1) mRNA and protein expression significantly, which may contribute to the inhibition of tumor growth by reactivation of antioxidative enzymes. This study advances our understanding of tumor growth inhibition by brewed GT in an animal model by demonstrating tissue localization of GTPs in correlation with inhibition of tumor growth. Our results suggest that the inhibition of tumor growth is due to GTP-mediated inhibition of oxidative stress and angiogenesis in the LAPC4 xenograft prostate tumor in SCID mice.
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