Modrianský Martin, Dvorák Zdenĕk
Institute of Medical Chemistry and Biochemistry, Palacký University, Hnevotínská 3, Olomouc, 775 15 Czech Republic.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005 Dec;149(2):213-5.
Microtubule disruptors, widely known as antimitotics, have broad applications in human medicine, especially as anti-neoplastic agents. They are subject to biotransformation within human body frequently involving cytochromes P450. Therefore antimitotics are potential culprits of drug-drug interactions on the level of activity as well as expression of cytochromes P450. This review discusses the effects of four well-known natural antimitotics: colchicine, taxol (paclitaxel), vincristine, and vinblastine, and a synthetic microtubule disruptor nocodazole on transcriptional activity of glucocorticoid and aryl hydrocarbon receptors. It appears that microtubules disarray restricts the signaling by these two nuclear receptors regardless of cell cycle phase. Consequently, intact microtubules play an important role in the regulation of expression of cytochromes P450, which are under direct or indirect control of the two nuclear receptors.
微管破坏剂，广为人知的抗有丝分裂剂，在人类医学中有广泛应用，尤其是作为抗肿瘤药物。它们在人体内常发生生物转化，这一过程频繁涉及细胞色素P450。因此，抗有丝分裂剂在细胞色素P450的活性水平以及表达方面，都是药物相互作用的潜在诱因。本综述讨论了四种著名的天然抗有丝分裂剂：秋水仙碱、紫杉醇、长春新碱和长春碱，以及一种合成微管破坏剂诺考达唑对糖皮质激素受体和芳烃受体转录活性的影响。似乎微管紊乱会限制这两种核受体的信号传导，而与细胞周期阶段无关。因此，完整的微管在细胞色素P450表达的调节中起着重要作用，而细胞色素P450受到这两种核受体的直接或间接控制。
