Iram Sana, Rahman Safikur, Ali Shahid, Kim Jihoe
Department of Medical Biotechnology and Research Institute of Cell Culture, Yeungnam University, Gyeongsan 38541, Republic of Korea.
Department of Botany, Munshi Singh College, BR Ambedkar Bihar University, Muzaffarpur, Bihar 845401, India.
Int J Biol Macromol. 2022 Jun 1;209(Pt A):211-219. doi: 10.1016/j.ijbiomac.2022.03.160. Epub 2022 Mar 28.
Tetranectin is a serum protein that binds to plasminogen and enhances its proteolytic activation, which underlies the involvement of tetranectin in the development of several carcinomas including colon cancer. In the present study, structure-based in silico screening of natural products showed that epigallocatechin gallate with anticancer effects binds to tetranectin. Binding to epigallocatechin gallate to tetranectin was confirmed by intrinsic fluorescence quenching assays and isothermal titration calorimetry. Furthermore, epigallocatechin gallate efficiently inhibited the activity of tetranectin to enhance the activation of plasminogen. We also found that tetranectin enhanced the proliferation of CT-26 colon cancer cells. Epigallocatechin gallate showed its cytotoxic effect on CT-26 cells due to its binding to tetranectin and the consequent suppression of the cell proliferation. These results demonstrate that the anticancer effect of epigallocatechin gallate is mediated, at least in part, by inhibiting tetranectin as a binding target.
纤连蛋白是一种血清蛋白，它与纤溶酶原结合并增强其蛋白水解激活作用，这是纤连蛋白参与包括结肠癌在内的多种癌症发生发展的基础。在本研究中，基于结构的天然产物虚拟筛选表明，具有抗癌作用的表没食子儿茶素没食子酸酯与纤连蛋白结合。通过内源荧光猝灭测定和等温滴定量热法证实了表没食子儿茶素没食子酸酯与纤连蛋白的结合。此外，表没食子儿茶素没食子酸酯有效抑制了纤连蛋白增强纤溶酶原激活的活性。我们还发现纤连蛋白促进了CT-26结肠癌细胞的增殖。表没食子儿茶素没食子酸酯由于与纤连蛋白结合并因此抑制细胞增殖，从而对CT-26细胞显示出细胞毒性作用。这些结果表明，表没食子儿茶素没食子酸酯的抗癌作用至少部分是通过抑制作为结合靶点的纤连蛋白来介导的。
