Geuens G M, Nuydens R M, Willebrords R E, Van de Veire R M, Goossens F, Dragonetti C H, Mareel M M, De Brabander M J
Cancer Res. 1985 Feb;45(2):733-42.
Light and electron microscopic investigations on mammalian cells in vitro and in vivo showed that tubulozole-C (R 46 846), the cis-isomer of tubulozole, a new synthetic anticancer drug, interfered with the structure and function of microtubules in both interphase and mitotic cells. The activity of this compound in experimental tumor systems can thus be explained partly by a direct antimitotic effect and partly by the disintegration of the normal subcellular organization of the nondividing cells. At concentrations which affect the microtubule system, tubulozole-C arrested directional migration of transformed cells and malignant invasion in a three-dimensional organ culture system. Investigations in vivo show that malignant L1210 leukemia cells are more susceptible to the antimicrotubular effect of tubulozole-C than are the normal leukocytes of the host. The trans-isomer of tubulozole (tubulozole-T, R 48 265), which has no antitumor activity in vivo, did not affect the microtubule system of cells in vitro or their capacity for directional migration or for malignant invasion.
对哺乳动物细胞进行的体外和体内光镜及电镜研究表明，新型合成抗癌药物tubulozole的顺式异构体tubulozole-C（R 46 846）在间期细胞和有丝分裂细胞中均会干扰微管的结构和功能。该化合物在实验性肿瘤系统中的活性，部分可由直接的抗有丝分裂作用来解释，部分可由非分裂细胞正常亚细胞组织的解体来解释。在影响微管系统的浓度下，tubulozole-C在三维器官培养系统中阻止了转化细胞的定向迁移和恶性侵袭。体内研究表明，恶性L1210白血病细胞比宿主的正常白细胞对tubulozole-C的抗微管作用更敏感。tubulozole的反式异构体（tubulozole-T，R 48 265）在体内没有抗肿瘤活性，在体外也不影响细胞的微管系统、定向迁移能力或恶性侵袭能力。
