PROMOTION OF MICROTUBULE ASSEMBLY INVITRO BY TAXOL
PROMOTION OF MICROTUBULE ASSEMBLY INVITRO BY TAXOL
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DOI：
10.1038/277665a0
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发表时间：
1979-01-01
期刊：
影响因子：
64.8
通讯作者：
HORWITZ, SB
中科院分区：
文献类型：
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作者：
SCHIFF, PB;FANT, J;HORWITZ, SB
紫杉醇(图1)是由Waniet等人从红豆杉(西部红豆杉)植物中分离出来的，他们报道了该分子在几个实验系统中具有抗肿瘤活性1。在我们的实验室中，我们发现紫杉醇，一种低分子量的中性化合物，在低浓度(0.25微米)的药物下完全抑制指数生长的HeLa细胞的分裂，而在与细胞孵育4小时期间，对DNA、RNA或蛋白质的合成没有显著影响。用紫杉醇孵育20h的HeLa细胞在G2和/或M期受阻(参考文献)。2)。我们在这里报道，紫杉醇在体外对小牛大脑微管组装起到促进作用，而秋水仙碱和鬼臼毒素等植物产品则抑制组装。紫杉醇减少微管组装的滞后时间，使微管组装的平衡向微管倾斜，从而降低组装所需的微管蛋白的临界浓度。在紫杉醇存在下聚合的微管耐冷(4℃)和CaCl2(4 Mm)解聚。
TAXOL (Fig. 1) was isolated from the plantTaxus brevifolia(western yew) by Waniet al., who reported that the molecule has antitumour activity in several experimental systems1. In our laboratory we have found that taxol, a low molecular weight neutral compound, completely inhibits division of exponentially growing HeLa cells at low concentrations of drug (0.25 µM) that have no significant effects on DNA, RNA or protein synthesis during a 4-h incubation with the cells. HeLa cells incubated with taxol for 20 h are blocked in late G2and/or M (ref. 2). We report here that taxol acts as a promoter of calf brain microtubule assemblyin vitro, in contrast to plant products such as colchicine and podophyllotoxin, which inhibit assembly. Taxol decreases the lag time for microtubule assembly and shifts the equilibrium for assembly in favour of the microtubule, thereby decreasing the critical concentration of tubulin required for assembly. Microtubules polymerised in the presence of taxol are resistant to depolymerisation by cold (4 °C) and CaCl2(4 mM).