College of Pharmacy, Pusan National University, Busan 46241, Korea.
State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China.
Mar Drugs. 2020 Aug 27;18(9):445. doi: 10.3390/md18090445.
Microtubules play a crucial role in mitosis and are attractive targets for cancer therapy. Recently, we isolated viriditoxin, a cytotoxic and antibacterial compound, from a marine fungus . Viriditoxin has been reported to inhibit the polymerization of bacterial FtsZ, a tubulin-like GTPase that plays an essential role in bacterial cell division. Given the close structural homology between FtsZ and tubulin, we investigated the potential antimitotic effects of viriditoxin on human cancer cells. Viriditoxin, like paclitaxel, enhanced tubulin polymerization and stabilized microtubule polymers, thereby perturbing mitosis in the SK-OV-3 cell line. However, the morphology of the stabilized microtubules was different from that induced by paclitaxel, indicating subtle differences in the mode of action of these compounds. Microtubule dynamics are also essential in cell movement, and viriditoxin repressed migration and colony formation ability of SK-OV-3 cells. Based on these results, we propose that viriditoxin interrupts microtubule dynamics, thus leading to antimitotic and antimetastatic activities.
微管在有丝分裂中起着至关重要的作用,是癌症治疗的有吸引力的靶点。最近,我们从一种海洋真菌中分离出了一种细胞毒素和抗菌化合物——绿毒素。绿毒素已被报道能抑制细菌 FtsZ 的聚合,FtsZ 是一种类似于微管的 GTP 酶,在细菌细胞分裂中起着至关重要的作用。鉴于 FtsZ 与微管之间的紧密结构同源性,我们研究了绿毒素对人类癌细胞的潜在抗有丝分裂作用。绿毒素与紫杉醇一样,增强了微管聚合并稳定了微管聚合物,从而扰乱了 SK-OV-3 细胞系中的有丝分裂。然而,稳定的微管的形态与紫杉醇诱导的不同,表明这些化合物的作用模式存在细微差异。微管动力学在细胞运动中也是必不可少的,绿毒素抑制了 SK-OV-3 细胞的迁移和集落形成能力。基于这些结果,我们提出绿毒素中断微管动力学,从而导致抗有丝分裂和抗转移活性。