Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells
Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells
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DOI：
10.1097/00001813-200106000-00009
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发表时间：
2001-06-01
影响因子：
2.3
通讯作者：
Claeson, P
中科院分区：
文献类型：
--
作者：
Johansson, S;Lindholm, P;Claeson, P
利用来自患者的肿瘤细胞原代培养物和人类细胞系面板（代表不同的细胞毒性耐药模式）评估了皂苷洋地黄苷、洋地黄苷元和五种心脏糖苷的细胞毒性。在这7种化合物中，原黄芩苷A的作用最强（IC50: 6.4-76 nM），其次是洋地黄素，然后是瓦巴因、地高辛、lanat苷C、洋地黄素和洋地黄素。对小组细胞系的对数IC50值的相关分析表明，化合物的细胞毒性仅受p糖蛋白、拓扑异构酶II、多药耐药相关蛋白和谷胱甘肽介导的耐药机制的轻微影响。地黄黄素和地高辛对来自患者的实体肿瘤细胞表现出选择性毒性，而原黄黄素A对实体或血液肿瘤细胞均无选择性毒性。结果显示，心脏糖苷的细胞毒性在效力和选择性上存在显著差异，其细胞毒性的作用方式也不同于常用的抗癌药物。[C] 2001 Lippincott Williams & Wilkins.]
The saponin digitonin, the aglycone digitoxigenin and five cardiac glycosides were evaluated for cytotoxicity using primary cultures of tumor cells from patients and a human cell line panel (representing different cytotoxic drug-resistance patterns). Of these seven compounds, proscillaridin A was the most potent (IC50: 6.4-76 nM), followed by digitoxin, and then ouabain, digoxin, lanatoside C, digitoxigenin and digitonin, Correlation analysis of the log IC50 values for the cell lines in the panel showed that compound cytotoxicity was only slightly influenced by resistance mechanisms that involved P-glycoprotein, topoisomerase II, multidrug resistance-associated protein and glutathione-mediated drug resistance. Digitoxin and digoxin expressed selective toxicity against solid tumor cells from patients, while proscillaridin A expressed no selective toxicity against either solid or hematological tumor cells. The results revealed marked differences in cytotoxicity between the cardiac glycosides, both in potency and selectivity, and modes of action for cytotoxicity that differ from that of commonly used anticancer drugs. [(C) 2001 Lippincott Williams & Wilkins.].