(-)-Epigallocatechin 3-Gallate Synthetic Analogues Inhibit Fatty Acid Synthase and Show Anticancer Activity in Triple Negative Breast Cancer.
(-)-Epigallocatechin 3-Gallate Synthetic Analogues Inhibit Fatty Acid Synthase and Show Anticancer Activity in Triple Negative Breast Cancer.
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DOI：
10.3390/molecules23051160
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发表时间：
2018-05-11
期刊：
影响因子：
--
通讯作者：
Puig T
中科院分区：
文献类型：
--
作者：
Crous-Masó J;Palomeras S;Relat J;Camó C;Martínez-Garza Ú;Planas M;Feliu L;Puig T
（−）-表没食子儿茶素没食子酸酯（EGCG）是一种来自绿色茶的天然多酚，据报道具有抗癌活性和抑制脂肪酸合成酶（FATCH）的能力，FATCH在几种人类癌症中过表达。为了改善EGCG的药理学特性，我们先前开发了一系列EGCG衍生物，并且在过表达FXR的HER 2阳性乳腺癌细胞中表征了先导化合物G28、G37和G56。在此，合成了二酯G28、G37和G56以及两种G28衍生物，单酯M1和M2，并在体外评估了它们在MDA-MB-231三阴性乳腺癌（TNBC）细胞中的细胞毒性、荧光素酶抑制和凋亡活性。所有化合物均表现出中度至高度的细胞毒性，并显著阻断Festival活性，单酯M1和M2是比二酯更有效的抑制剂。有趣的是，G28，M1和M2也降低了Fatty acid蛋白的表达水平，但只有单酯M1和M2诱导细胞凋亡。我们的研究结果表明，这种多酚类化合物对FcB的抑制可能是TNBC治疗的新策略，并突出了单酯的潜在抗癌活性。因此，G28、G37、G56以及最重要的M1和M2是待进一步在体外和体内表征的抗癌候选物（单独或组合）。
(−)-Epigallocatechin 3-gallate (EGCG) is a natural polyphenol from green tea with reported anticancer activity and capacity to inhibit the lipogenic enzyme fatty acid synthase (FASN), which is overexpressed in several human carcinomas. To improve the pharmacological profile of EGCG, we previously developed a family of EGCG derivatives and the lead compounds G28, G37 and G56 were characterized in HER2-positive breast cancer cells overexpressing FASN. Here, diesters G28, G37 and G56 and two G28 derivatives, monoesters M1 and M2, were synthesized and assessed in vitro for their cytotoxic, FASN inhibition and apoptotic activities in MDA-MB-231 triple-negative breast cancer (TNBC) cells. All compounds displayed moderate to high cytotoxicity and significantly blocked FASN activity, monoesters M1 and M2 being more potent inhibitors than diesters. Interestingly, G28, M1, and M2 also diminished FASN protein expression levels, but only monoesters M1 and M2 induced apoptosis. Our results indicate that FASN inhibition by such polyphenolic compounds could be a new strategy in TNBC treatment, and highlight the potential anticancer activities of monoesters. Thus, G28, G37, G56, and most importantly M1 and M2, are anticancer candidates (alone or in combination) to be further characterized in vitro and in vivo.
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影响因子：
3.8
作者：
Relat J;Blancafort A;Oliveras G;Cufí S;Haro D;Marrero PF;Puig T
通讯作者：
Puig T
影响因子：
29
作者：
Pavlova NN;Thompson CB
通讯作者：
Thompson CB
双脂肪酸合酶和HER2信号阻滞显示出针对抗抗HEH2药物的乳腺癌模型的明显抗肿瘤活性。
影响因子：
3.7
作者：
Blancafort A;Giró-Perafita A;Oliveras G;Palomeras S;Turrado C;Campuzano Ò;Carrión-Salip D;Massaguer A;Brugada R;Palafox M;Gómez-Miragaya J;González-Suárez E;Puig T
通讯作者：
Puig T
影响因子：
--
作者：
Giró-Perafita A;Sarrats A;Pérez-Bueno F;Oliveras G;Buxó M;Brunet J;Viñas G;Miquel TP
通讯作者：
Miquel TP
影响因子：
56.9
作者：
Maier, Timm;Leibundgut, Marc;Ban, Nenad
通讯作者：
Ban, Nenad