Department of Biotechnology and Dr. B. C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, WB 700019, India.
Department of Biotechnology and Dr. B. C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, WB 700019, India.
Chem Biol Interact. 2015 Dec 5;242:380-9. doi: 10.1016/j.cbi.2015.11.004. Epub 2015 Nov 7.
In this study our main objective was to find out a novel target of the major bioactive green tea polyphenol, Epigallocatechin-3-gallate (EGCG), in cervical carcinoma HeLa cells. We found that EGCG showed antiproliferative activity against HeLa cells through depolymerization of cellular microtubule. EGCG also prevented the reformation of the cellular microtubule network distorted by cold treatment and inhibited polymerization of tubulin in cell-free system with IC50 of 39.6 ± 0.63 μM. Fluorescence spectroscopic analysis showed that EGCG prevented colchicine binding to tubulin and in silico study revealed that EGCG bound to the α-subunit of tubulin at the interphase of the α-and β-heterodimers and very close to colchicine binding site. The binding is entropy driven (ΔS(0) was 18.75 ± 1.48 cal K(-1) mol(-1)) with Kd value of 3.50 ± 0.40 μM. This is a novel mechanism of antipriliferative activity of EGCG.
在这项研究中，我们的主要目标是在宫颈癌 HeLa 细胞中找到主要生物活性绿茶多酚表没食子儿茶素没食子酸酯 (EGCG) 的新靶标。我们发现 EGCG 通过细胞微管的解聚对 HeLa 细胞表现出抗增殖活性。EGCG 还可以防止冷处理扭曲的细胞微管网络的重新形成，并抑制无细胞体系中微管蛋白的聚合，IC50 为 39.6±0.63 μM。荧光光谱分析表明，EGCG 可阻止秋水仙碱与微管蛋白结合，计算研究表明 EGCG 与微管蛋白的α-亚基结合，位于α-和β-异二聚体的界面上，并且非常接近秋水仙碱结合位点。这种结合是熵驱动的（ΔS(0) 为 18.75±1.48 cal K(-1) mol(-1)），Kd 值为 3.50±0.40 μM。这是 EGCG 抗增殖活性的新机制。
