Eleutherobin, a novel cytotoxic agent that induces tubulin polymerization, is similar to paclitaxel (Taxol).
Eleutherobin, a novel cytotoxic agent that induces tubulin polymerization, is similar to paclitaxel (Taxol).
复制标题
DOI：
--
复制
发表时间：
1998-03
期刊：
影响因子：
11.2
通讯作者：
Byron H. Long;Joan M. Carboni;Arthur J. Wasserman;Laurie Cornell;A. Casazza;Paul R. Jensen;Thomas Lindel;W. Fenical;Craig R. Fairchild
中科院分区：
文献类型：
--
作者：
Byron H. Long;Joan M. Carboni;Arthur J. Wasserman;Laurie Cornell;A. Casazza;Paul R. Jensen;Thomas Lindel;W. Fenical;Craig R. Fairchild
五加素是一种从海洋软珊瑚中分离出来的新型天然产物，其在体外诱导微管蛋白聚合的能力非常强，并且对癌细胞具有细胞毒性，其IC 50与紫杉醇相似。该化合物与其他多药耐药药物一起对P-糖蛋白表达细胞具有交叉耐药，并且与紫杉醇对微管蛋白改变的细胞系具有交叉耐药。沿着。在机制研究中，刺五加苷酶与紫杉醇共享在体外诱导微管蛋白聚合的能力，并且最有可能由于该机制而具有细胞毒性。暴露于五加素的人结肠癌细胞含有多个微核和微管束，并且它们在有丝分裂中停滞，这取决于浓度、细胞系和暴露时间。这些形态异常出现在培养的细胞是无法区分的紫杉醇诱导。电子显微镜显示，eleutherobin诱导长，刚性微管类似于那些由紫杉醇形成的均匀群体。因此，刺五加苷是一种新的化学型，其作用机制与紫杉醇相似，因此，具有作为新抗癌剂的潜力。
Eleutherobin is a novel natural product isolated from a marine soft coral that is extremely potent for inducing tubulin polymerization in vitro and is cytotoxic for cancer cells with an IC50 similar to that of paclitaxel. This compound is cross-resistant along with other multidrug-resistant agents against P-glycoprotein-expressing cells and is cross-resistant with paclitaxel against a cell line that has altered tubulin. In mechanistic studies, eleutherobin shares with paclitaxel the ability to induce tubulin polymerization in vitro and is most likely cytotoxic by virtue of this mechanism. Human colon carcinoma cells exposed to eleutherobin contain multiple micronuclei and microtubule bundles, and they arrest in mitosis, depending on concentration, cell line, and length of exposure. These morphological abnormalities appearing in cultured cells are indistinguishable from those induced by paclitaxel. Electron microscopy reveals that eleutherobin induces homogeneous populations of long, rigid microtubules similar to those formed by paclitaxel. Thus, eleutherobin is a new chemotype with a mechanism of action similar to that of paclitaxel and, as such, has promising potential as a new anticancer agent.