Nakamura Machiko, Nakazawa Junko, Usui Takeo, Osada Hiroyuki, Kono Yoshiki, Takatsuki Akira
Animal and Cellular Systems Laboratory, RIKEN, Institute of Physical and Chemical Research, Hirosawa 2-1, Wako-shi, Saitama 351-0198, Japan.
Biosci Biotechnol Biochem. 2003 Jan;67(1):151-7. doi: 10.1271/bbb.67.151.
Nordihydroguaiaretic acid (NDGA) protected microtubules in NRK cells from depolymerization caused by structurally and functionally diverse drugs such as nocodazole, colchicine, vinblastine, and ilimaquinone. Hitherto reported drugs, although structurally unrelated to paclitaxel, stabilize microtubules in a way similar to that of paclitaxel and compete for paclitaxel binding to tubulin. However, NDGA had activity toward microtubules different from the effects of paclitaxel. In NRK cells, paclitaxel caused microtubule bundle formation in the presence and absence of microtubule-depolymerizing drugs. However, microtubule bundle did not form, and microtubules radiated from the microtubule-organizing center, in cells treated with NDGA. Acceleration of tubulin polymerization in vitro by paclitaxel was strong but that by NDGA was weak. Microtubules polymerized in vitro in the presence of paclitaxel, but not those polymerized in the presence of NDGA, resisted the effects of cold. NDGA seemed to bind to tubulin, but did not compete for [3H]paclitaxel binding to tubulin. These observations indicate that NDGA belongs to a novel family of microtubule-stabilizing drugs.
去甲二氢愈创木酸（NDGA）可保护NRK细胞中的微管，使其免受诸如诺考达唑、秋水仙碱、长春碱和伊立马喹酮等结构和功能各异的药物所导致的解聚作用。迄今报道的药物，尽管在结构上与紫杉醇无关，但它们以类似于紫杉醇的方式稳定微管，并竞争紫杉醇与微管蛋白的结合。然而，NDGA对微管的作用不同于紫杉醇的作用。在NRK细胞中，无论有无微管解聚药物存在，紫杉醇都会导致微管束的形成。然而，在用NDGA处理的细胞中，微管束并未形成，微管从微管组织中心呈放射状分布。紫杉醇在体外对微管蛋白聚合的促进作用很强，而NDGA的促进作用较弱。在紫杉醇存在的情况下，微管在体外聚合，但在NDGA存在下聚合的微管则不能抵抗低温的影响。NDGA似乎能与微管蛋白结合，但并不竞争[3H]紫杉醇与微管蛋白的结合。这些观察结果表明，NDGA属于一类新型的微管稳定药物。
