Catechin conjugated with fatty acid inhibits DNA polymerase and angiogenesis
Catechin conjugated with fatty acid inhibits DNA polymerase and angiogenesis
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DOI：
10.1089/dna.2006.25.95
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发表时间：
2006-02-01
影响因子：
3.1
通讯作者：
Mizushina, Y
中科院分区：
文献类型：
--
作者：
Matsubara, K;Saito, A;Mizushina, Y
绿色茶中的儿茶素具有抗癌和抗血管生成活性，其中表没食子儿茶素-3-没食子酸酯（epigallocatechin-3-gallate，EGCG）是最有效的抗血管生成茶儿茶素。本研究探讨了儿茶素的化学修饰是否增强了抗癌和抗血管生成的作用。儿茶素与脂肪酸（酰基儿茶素）结合，强烈抑制DNA聚合酶，HL-60癌细胞生长和血管生成。与硬脂酸缀合的儿茶素[（2 R，3S）-3 '，4'，5，7-四羟基黄烷-3-基十八烷酸酯;儿茶素-C18]在DNA聚合酶α和β以及血管生成测定中是最强的抑制剂。儿茶素-C18还抑制人内皮细胞（HUVEC）在重建基底膜上的管形成，这表明它不仅影响DNA聚合酶，而且影响HUVEC中的信号转导通路。这些数据表明酰基儿茶素靶向DNA聚合酶和血管生成作为抗癌剂。这些结果表明，儿茶素的酰化是提高儿茶素抗癌活性的有效化学修饰方法。
Catechins in green tea have anticancer and antiangiogenesis activities, with epigallocatechin-3-gallate (EGCG) being the most potent antiangiogenic tea catechin. This study examined whether chemical modification of catechin enhanced anticancer and antiangiogenic effects. Catechin, conjugated with fatty acid (acyl-catechin), strongly inhibited DNA polymerase, HL-60 cancer cell growth, and angiogenesis. Catechin conjugated with stearic acid [(2R, 3S)-3',4',5,7-tetrahydroxyflavan-3-yl octadecanoate; catechin-C18] was the strongest inhibitor in DNA polymerase alpha and beta and angiogenesis assays. Catechin-C18 also suppressed human endothelial cell (HUVEC) tube formation on the reconstituted basement membrane, suggesting that it affected not only DNA polymerases but also signal transduction pathways in HUVECs. These data indicate that acyl-catechins target both DNA polymerases and angiogenesis as anticancer agents. These results suggest that acylation of catechin is an effective chemical modification to improve the anticancer activity of catechin.