Szekely J G, Lobreau A U, Delaney S, Raaphorst G P, Feeley M
Radiation Applications Research Branch, Atomic Energy of Canada Limited Research Company, Whiteshell Nuclear Research Establishment, Pinawa, MB, Canada.
Scanning Microsc. 1989 Jun;3(2):681-91; discussion 691-3.
Lonidamine, 1-(2-4-dichlorobenzyl)-1-H-indazol-3-carboxylic acid, is an anticancer drug that has its primary action on cellular metabolism rather than cell division. Since lonidamine is not effective in all tumor cells, we have tested it in two human-tumor cell culture lines: MOLT-4, a T-leukemia and U-87 MG, a glioma. Lonidamine exposure of MOLT-4 cells at 50 micrograms/mL and pH 6.7 disrupted the mitochondria within 1 h of treatment. The mitochondria were swollen and the cristae were disrupted. When the treated cells were re-incubated in fresh medium at pH 7.4 the mitochondria rapidly returned to their normal morphology. The U-87 MG glioma cells did not show ultrastructural disruption after 1-h treatment with lonidamine at concentrations up to 200 micrograms/mL at pH 6.7. In the concentration range of 25 micrograms/mL to 200 micrograms/mL, lonidamine did not produce any cell killing in MOLT-4 after a 1-h exposure at pH 7.4, although the drug had some limited effectiveness at pH 6.7. Compared to sham-treated controls, long exposures to 100 micrograms/mL of lonidamine at pH 6.7 reduced survival in MOLT-4 to 92% and 53% after 6-h and 24-h exposures, respectively. Survival of U-87 MG glioma cells was also strongly pH dependent, a 2-h exposure to 50 micrograms/mL lonidamine at pH 7.4 did not cause cell death; however, survival dropped to 84% of the control at pH 6.65.
氯尼达明，即1-(2,4-二氯苄基)-1-H-吲唑-3-羧酸，是一种抗癌药物，其主要作用于细胞代谢而非细胞分裂。由于氯尼达明并非对所有肿瘤细胞都有效，我们在两种人肿瘤细胞系中对其进行了测试：MOLT-4，一种T淋巴细胞白血病细胞系，以及U-87 MG，一种神经胶质瘤细胞系。在pH 6.7条件下，用50微克/毫升的氯尼达明处理MOLT-4细胞1小时后，线粒体遭到破坏。线粒体肿胀，嵴被破坏。当将处理后的细胞在pH 7.4的新鲜培养基中重新孵育时，线粒体迅速恢复其正常形态。在pH 6.7条件下，用浓度高达200微克/毫升的氯尼达明处理U-87 MG神经胶质瘤细胞1小时后，未观察到超微结构破坏。在25微克/毫升至200微克/毫升的浓度范围内，在pH 7.4条件下，氯尼达明处理MOLT-4细胞1小时后未产生任何细胞杀伤作用，尽管该药物在pH 6.7时有一定的有限效果。与假处理对照组相比，在pH 6.7条件下长时间暴露于100微克/毫升的氯尼达明，MOLT-4细胞在暴露6小时和24小时后的存活率分别降至92%和53%。U-87 MG神经胶质瘤细胞的存活率也强烈依赖于pH值，在pH 7.4条件下用50微克/毫升氯尼达明处理2小时不会导致细胞死亡；然而，在pH 6.65时，存活率降至对照组的84%。
