Tohyama Shigehiro, Kawada Manabu, Muramatsu Hideyuki, Hatano Masaki, Inoue Hiroyuki, Matoba Kazuaki, Sawa Ryuichi, Igarashi Masayuki
Institute of Microbial Chemistry, Microbial Chemistry Research Foundation (BIKAKEN), Shinagawa-ku, Tokyo, Japan.
J Antibiot (Tokyo). 2021 Oct;74(10):743-751. doi: 10.1038/s41429-021-00455-w. Epub 2021 Jul 21.
Specific inhibitors of protein phosphatase 2A (PP2A) mediate anticancer effects by augmenting the tumor-killing activity of natural killer (NK) cells. In this study, new PP2A inhibitors, aminocytostatins A-E, were isolated from Kitasatospora sp. MJ654-NF4 and structurally characterized. Aminocytostatins are derivatives of cytostatin, which is a specific PP2A inhibitor isolated from the same organism, and aminocytostatins have a characteristic amino group within the lactone moiety. Compared to cytostatin, aminocytostatin A showed a stronger inhibitory activity against PP2A in vitro and augmented the tumor-killing activity of NK cells in vivo. Furthermore, a docking model was generated to demonstrate the favorable activities of aminocytostatin A.
蛋白磷酸酶2A（PP2A）的特异性抑制剂通过增强自然杀伤（NK）细胞的肿瘤杀伤活性来介导抗癌作用。在本研究中，从北里孢菌属MJ654-NF4中分离出新型PP2A抑制剂氨基制癌菌素A-E，并对其进行了结构表征。氨基制癌菌素是制癌菌素的衍生物，制癌菌素是从同一生物体中分离出的一种特异性PP2A抑制剂，氨基制癌菌素在内酯部分含有一个特征性氨基。与制癌菌素相比，氨基制癌菌素A在体外对PP2A表现出更强的抑制活性，并在体内增强了NK细胞的肿瘤杀伤活性。此外，还构建了一个对接模型来证明氨基制癌菌素A的良好活性。
