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首页> 外文期刊>Journal of cellular biochemistry. >Biological and Mechanistic Characterization of Novel Prodrugs of Green Tea Polyphenol Epigallocatechin Gallate Analogs in Human Leiomyoma Cell Lines
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Biological and Mechanistic Characterization of Novel Prodrugs of Green Tea Polyphenol Epigallocatechin Gallate Analogs in Human Leiomyoma Cell Lines

机译：新型绿茶多酚表没食子儿茶素没食子酸酯没食子酸酯类似物在人平滑肌瘤细胞系中的生物学和机制表征。

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Uterine fibroids (leiomyomas) are very common benign tumors grown on the smooth muscle layer of the uterus, present in up to 75% of reproductive-age women and causing significant morbidity in a subset of this population. Although the etiology and biology of uterine fibroids are unclear, strong evidence supports that cell proliferation, angiogenesis and fibrosis are involved in their formation and growth. Currently the only cure for uterine fibroids is hysterectomy; the available alternative therapies have limitations. Thus, there is an urgent need for developing a novel strategy for treating this condition. The green tea polyphenol epigallocatechin gallate (EGCG) inhibits the growth of uterine leiomyoma cells in vitro and in vivo, and the use of a green tea extract (containing 45% EGCG) has demonstrated clinical activity without side effects in women with symptomatic uterine fibroids. However, EGCG has a number of shortcomings, including low stability, poor bioavailability, and high metabolic transformations under physiological conditions, presenting challenges for its development as a therapeutic agent. We developed a prodrug of EGCG (Pro-EGCG or 1) which shows increased stability, bioavailability and biological activity in vivo as compared to EGCG. We also synthesized prodrugs of EGCG analogs, compounds 2a and 4a, in order to potentially reduce their susceptibility to methylation/inhibition by catechol-O-methyltransferase. Here, we determined the effect of EGCG, Pro-EGCG, and 2a and 4a on cultured human uterine leiomyoma cells, and found that 2a and 4a have potent antiproliferative, antiangiogenic, and antifibrotic activities. J. Cell. Biochem. 117: 2357-2369, 2016. (c) 2016 Wiley Periodicals, Inc.
机译：子宫肌瘤（平滑肌瘤）是在子宫平滑肌层上生长的非常常见的良性肿瘤，存在于多达75％的育龄妇女中，并在这一人群的一部分中引起明显的发病率。尽管子宫肌瘤的病因和生物学尚不清楚，但有力的证据支持细胞增殖，血管生成和纤维化参与其形成和生长。目前，子宫肌瘤的唯一治疗方法是子宫切除术。现有的替代疗法有局限性。因此，迫切需要开发一种用于治疗该病症的新策略。绿茶多酚表没食子儿茶素没食子酸酯（EGCG）在体外和体内均能抑制子宫平滑肌瘤细胞的生长，绿茶提取物（含45％EGCG）的使用已证明其临床活性对有症状子宫肌瘤的女性无副作用。然而，EGCG具有许多缺点，包括稳定性低，生物利用度差以及在生理条件下的高代谢转化，这给其作为治疗剂的发展提出了挑战。我们开发了EGCG的前药（Pro-EGCG或1），与EGCG相比，它在体内显示出更高的稳定性，生物利用度和生物活性。我们还合成了EGCG类似物的前药，化合物2a和4a，以潜在地降低其对儿茶酚-O-甲基转移酶的甲基化/抑制作用的敏感性。在这里，我们确定了EGCG，Pro-EGCG以及2a和4a对培养的人子宫平滑肌瘤细胞的作用，并发现2a和4a具有有效的抗增殖，抗血管生成和抗纤维化活性。 J.细胞。生化。 117：2357-2369，2016。（c）2016 Wiley Periodicals，Inc.

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