Antimitochondrial Drugs in Cancer Chemotherapy: Preliminary Communication
Antimitochondrial Drugs in Cancer Chemotherapy: Preliminary Communication
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抗线粒体药物在癌症化疗中的应用：初步交流
DOI：
10.1177/014107687907200810
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发表时间：
1979
影响因子：
17.3
通讯作者：
D. Wilkie
中科院分区：
文献类型：
--
作者：
D. Wilkie
在酵母细胞的初步研究中，发现抗抑郁药氯丙咪嗪（Anafranil，CIBA-Geigy）和抗麻风病药物氯法齐明（Lamprene，CIBA-Geigy）的主要靶点是麻风杆菌（Hughes & Wilkie 1970，罗兹& Wilkie 1973）。两种药物都抑制呼吸链，但机制不同。离体大鼠肝线粒体的氧摄取的影响，以类似的方式完整的酵母线粒体。当这些研究扩展到人皮肤成纤维细胞培养物时（Wilkie & Delhanty 1970，Delhanty et al. 1974，Mittwoch & Wilkie 1971），两种药物再次对人细胞中的氧摄取产生直接影响，类似于酵母细胞中的氧摄取。这一系列实验的重要发现是SV-40转化细胞（癌症类型）比非转化成纤维细胞更容易受到药物抑制作用的影响。氯丙咪嗪对转化细胞的结果包括在上述参考文献中，而氯法齐明的结果表明，培养基中约2 μ g/ml是转化成纤维细胞的致死剂量，但杀死非转化培养物需要约8 μ g/ml（未发表的结果）。注意到在氧电极研究中转化细胞的呼吸速率显著低于它们的正常对应物（Wilkie & Delhanty 1970）。这些结果表明，通过用抗线粒体剂处理，在癌型细胞中抑制线粒体活性（已经很低）杀死这些细胞，而正常细胞可以从这种处理中恢复。
In initial studies with yeast cells it was found that the primary target of the antidepressant chlorimipramine (Anafranil, CIBA-Geigy) and the anti-leprosy drug clofazimine (Lamprene, CIBA-Geigy) was the mitochondrion (Hughes & Wilkie 1970, Rhodes & Wilkie 1973). Both drugs inhibited the respiratory chain, although by different mechanisms. The oxygen uptake of isolated rat liver mitochondria was affected in a similar way to that of the intact yeast mitochondria. When these studies were extended to human skin fibroblast cultures (Wilkie & Delhanty 1970, Delhanty et al. 1974, Mittwoch & Wilkie 1971), both drugs again had a direct effect on oxygen uptake in the human cells similar to that in yeast cells. The significant finding in this series of experiments was that SV-40 transformed cells (cancer type) were much more susceptible to the inhibitory effects of the drugs than the non-transformed fibroblasts. Results with chlorimipramine on transformed cells are included in the above references, while clofazimine results showed that about 2 jsg/ml in the culture medium was a lethal dose for transformed fibroblasts but about 8 jig/ml was required to kill non-transformed cultures (unpublished results). It was noted that the respiratory rate of transformed cells was significantly less than their normal counterparts in oxygen electrode studies (Wilkie & Delhanty 1970). These results indicated that depression of mitochondrial activity (already low), in the cancer type cells, by treatment with antimitochondrial agents kills these cells, while normal cells can recover from this treatment.