School of Pharmacy, Nanjing Medical University, Nanjing, 211166, People's Republic of China.
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing, 211166, People's Republic of China.
J Nat Prod. 2022 Aug 26;85(8):1918-1927. doi: 10.1021/acs.jnatprod.1c01215. Epub 2022 Aug 11.
Interference of microtubule dynamics with tubulin-targeted drugs is a validated approach for cancer chemotherapy. Moroidin () is an Urticaceae-type cyclopeptide having a potent inhibitory effect on purified tubulin polymerization. So far, moroidin has not been chemically synthesized, and its effect on cancer cells remains unknown. Herein, the cyclopeptide moroidin was isolated and identified from the seeds of , and a revised assignment of its NMR data was presented. For the first time, moroidin () was demonstrated as having cytotoxic effects for several cancer cells, especially A549 lung cancer cells. The cellular evidence obtained showed that moroidin disrupts microtubule polymerization and decreases β-tubulin protein levels, but is not as potent as colchicine. Molecular docking indicated that has a high binding potential to the vinca alkaloid site on tubulin. Moreover, moroidin arrested A549 cells in the G2/M phase and induced cell apoptosis. The intrinsic mitochondrial pathway and AKT were involved in the moroidin-induced cell apoptosis. In addition, moroidin () inhibited the migration and invasion of A549 cells at sublethal concentrations.
微管动力学与微管靶向药物的干扰是癌症化疗的一种有效方法。莫罗丁（）是一种荨麻科环肽，对纯化的微管聚合具有很强的抑制作用。到目前为止，莫罗丁还没有经过化学合成，其对癌细胞的作用尚不清楚。本文从的种子中分离并鉴定出环肽莫罗丁，并对其 NMR 数据进行了修正。莫罗丁（）首次被证明对多种癌细胞具有细胞毒性作用，特别是 A549 肺癌细胞。获得的细胞证据表明，莫罗丁破坏微管聚合并降低β-微管蛋白水平，但不如秋水仙碱有效。分子对接表明，对微管上的长春花生物碱结合位点具有高结合潜力。此外，莫罗丁将 A549 细胞阻滞在 G2/M 期并诱导细胞凋亡。内在的线粒体途径和 AKT 参与了莫罗丁诱导的细胞凋亡。此外，莫罗丁（）在亚致死浓度下抑制 A549 细胞的迁移和侵袭。
