Alvarez-Rodríguez Y, Ruano A, Alvarez-Noves J, Valladares Y
Departament of Biology and Biochemistry of Cancer, Instituto Nacional de Oncología, Madrid.
Rev Esp Oncol. 1985;32(3):383-410.
This work deals with the effect of thiazolidine-4-carboxylic acid (thioproline) upon several in vitro established human cell lines. Times-lapse microcinematography is used to study the action of thioproline on HeLa cells, employing high doses during a short time, and continuous exposure to medium and small doses. The effect of thioproline in mixed cultures of HeLa cells and human lymphoblasts is described. Special attention is paid to the observed cell cycle phase specificity, and to the phenomenon described as reverse transformation that has been associated to the drug. Marked differences is the sensitivity to thioproline are observed for the different types of in vitro established cell lines. The effect is always produced during the G1 and S phases of the cell cycle. Cell changes are produced only after contacting with one another, and the biochemical reactions which are proper of cell contact inhibition of growth and/or genotypic reverse transformation were never observed, so that the mechanism of action of the drug has to be revised. From a morphodynamic point of view, thioproline is an interesting drug because it produces peculiar effects which differ markedly from those produced by the other cancer chemotherapy agents. Thioproline could prove to be useful for cancer chemotherapy if used in combination with other drugs, knowing that it is a low activity phase specific antineoplastic drug and not a drug producing reverse transformation.
这项工作研究了噻唑烷 - 4 - 羧酸(硫代脯氨酸)对几种体外建立的人类细胞系的影响。采用延时显微电影摄影术来研究硫代脯氨酸对HeLa细胞的作用,在短时间内使用高剂量,并持续暴露于中低剂量。描述了硫代脯氨酸在HeLa细胞与人淋巴母细胞混合培养物中的作用。特别关注观察到的细胞周期阶段特异性,以及与该药物相关的被称为逆向转化的现象。观察到不同类型的体外建立的细胞系对硫代脯氨酸的敏感性存在显著差异。这种作用总是在细胞周期的G1期和S期产生。细胞变化仅在彼此接触后才会出现,并且从未观察到细胞接触抑制生长和/或基因型逆向转化所特有的生化反应,因此必须对该药物的作用机制进行修正。从形态动力学的角度来看,硫代脯氨酸是一种有趣的药物,因为它产生的特殊效应与其他癌症化疗药物产生的效应明显不同。已知硫代脯氨酸是一种低活性阶段特异性抗肿瘤药物,而非产生逆向转化的药物,如果与其他药物联合使用,它可能被证明对癌症化疗有用。