Maehara Y, Kusumoto H, Anai H, Kusumoto T, Sugimachi K
Cancer Center of Kyushu University Hospital, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Oncology. 1988;45(3):187-91. doi: 10.1159/000226559.
The effects of Vinca alkaloids, vinblastine, vincristine, and vindesine, on protein synthesis were determined using HeLa cells. Vinblastine at the concentration of 1 microgram/ml induced new proteins, isoelectric points 4.8 and 7.0-7.5 and molecular weights 48 and 92 kd, in the HeLa cells, identified using two-dimensional gel electrophoresis. The 48-kd and the clustered (4-components) 92-kd proteins were also noted in HeLa cells treated with vincristine or vindesine. As most of the 48- and 92-kd proteins were Triton insoluble, they can be considered components of the cytoskeletal structure. Syntheses of these proteins were blocked by actinomycin D, therefore, new messenger RNA synthesis is required for induction. These proteins were not induced by an alkylating agent, antitumor antibiotics, or an antimetabolite. Our findings show that the 48- and the clustered 92-kd proteins are Vinca alkaloid reactive components and can be considered candidates for the elucidation of the antineoplastic effect of Vinca alkaloids.
利用海拉细胞测定了长春花生物碱、长春碱、长春新碱和长春地辛对蛋白质合成的影响。浓度为1微克/毫升的长春碱在海拉细胞中诱导产生了新的蛋白质,其等电点为4.8以及7.0 - 7.5,分子量为48千道尔顿和92千道尔顿,通过二维凝胶电泳鉴定。在用长春新碱或长春地辛处理的海拉细胞中也观察到了48千道尔顿的蛋白质以及成簇的(4个组分)92千道尔顿的蛋白质。由于大多数48千道尔顿和92千道尔顿的蛋白质不溶于曲拉通,它们可被视为细胞骨架结构的组分。这些蛋白质的合成被放线菌素D阻断,因此,诱导需要新的信使核糖核酸合成。这些蛋白质不会被烷化剂、抗肿瘤抗生素或抗代谢物诱导产生。我们的研究结果表明,48千道尔顿的蛋白质和成簇的92千道尔顿的蛋白质是长春花生物碱反应性组分,可被视为用于阐明长春花生物碱抗肿瘤作用的候选物质。