Lampidis T J, Hasin Y, Weiss M J, Chen L B
Biomed Pharmacother. 1985;39(5):220-6.
Lipophilic positively-charged compounds are facilitated across biological membranes by the transmembrane potential of intact cells. One such compound, rhodamine 123, has recently been shown to be selectively toxic toward a variety of transformed (carcinoma), epithelial cells in vitro (Lampidis et al., 1982; Bernal et al., 1982; Lampidis et al., 1983). A mechanism that could account for the selectivity of this agent would be a difference in the plasma membrane potential between normal and carcinoma cells. We report here that a significantly higher transmembrane potential has been found in a pair of carcinoma (83 mV for human breast and -99 mV for human cervix) as compared to normal (-56 mV for marsupial kidney and -48 mV for monkey kidney) epithelial cell lines. We also identified 3 other positively-charged lipophilic compounds, safranin 0, rhodamine 6G and tetraphenylphosphonium chloride (TPP+), which show selective toxicity toward carcinoma cells in vitro, while an uncharged lipophilic analog, rhodamine 116, does not. These data suggest that the higher plasma membrane potential of carcinoma cells may in part contribute to the preferential accumulation and selective toxicity of the lipophilic cationic compounds we have examined. An extension of this concept to an in vivo environment could lead to a class of cationic compounds which selectively exploit differences between normal and carcinoma cells.
亲脂性带正电荷的化合物可借助完整细胞的跨膜电位穿过生物膜。一种这样的化合物，罗丹明123，最近已被证明在体外对多种转化的（癌）上皮细胞具有选择性毒性（兰皮迪斯等人，1982年；贝尔纳尔等人，1982年；兰皮迪斯等人，1983年）。一种可以解释这种药物选择性的机制可能是正常细胞和癌细胞之间质膜电位的差异。我们在此报告，与正常上皮细胞系（有袋动物肾脏为-56 mV，猴肾为-48 mV）相比，在一对癌细胞系（人乳腺癌为83 mV，人宫颈癌为-99 mV）中发现了显著更高的跨膜电位。我们还鉴定出另外3种带正电荷的亲脂性化合物，番红O、罗丹明6G和四苯基氯化鏻（TPP+），它们在体外对癌细胞表现出选择性毒性，而一种不带电荷的亲脂性类似物罗丹明116则没有。这些数据表明，癌细胞较高的质膜电位可能部分促成了我们所研究的亲脂性阳离子化合物的优先积累和选择性毒性。将这一概念扩展到体内环境可能会产生一类选择性利用正常细胞和癌细胞之间差异的阳离子化合物。
