Dequalinium induces a selective depletion of mitochondrial DNA from HeLa human cervical carcinoma cells.
Dequalinium induces a selective depletion of mitochondrial DNA from HeLa human cervical carcinoma cells.
复制标题
Dequalinium 诱导 HeLa 人宫颈癌细胞线粒体 DNA 的选择性耗尽。
DOI：
10.1006/excr.1998.4236
复制
发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Rowe,TC
中科院分区：
文献类型：
--
作者：
SchneiderBerlin,KR;Ammini,CV;Rowe,TC
用抗癌药物地喹铵（DEQ）处理培养的人宫颈癌细胞，发现会引起细胞生长的延迟抑制。这种抑制之前会出现线粒体DNA（mtDNA）的丢失、细胞色素氧化酶活性的降低和乳酸水平的增加，这表明生长抑制是由于线粒体DNA编码功能的丧失。在DEQ存在的情况下，每次细胞分裂后线粒体DNA的损失都是进行性的两倍，这表明这种药物通过抑制线粒体DNA合成的某些方面发挥作用。此外，当细胞在绕过mtDNA编码功能的条件下生长时，它们对DEQ的生长抑制和细胞毒性作用具有抗性。耐药性与药物蓄积的显著变化无关。这些结果表明，DEQ诱导的mtDNA耗竭在药物细胞毒性中起重要作用。
Treatment of cultured human cervical carcinoma cells with the anticancer drug dequalinium (DEQ) was found to cause a delayed inhibition of cell growth. This inhibition was preceded by a loss of mitochondrial DNA (mtDNA), a decrease in cytochromecoxidase activity, and an increase in the level of lactate, indicating that growth inhibition was due to the loss of mtDNA-encoded functions. There was a progressive two-fold loss of mtDNA following each cell division in the presence of DEQ, suggesting that this drug was acting by inhibiting some aspect of mtDNA synthesis. Furthermore, cells became resistant to the growth inhibitory and cytotoxic affects of DEQ when they were grown under conditions that bypassed the need for mtDNA-encoded functions. Resistance was not associated with significant changes in drug accumulation. These results suggest that the DEQ-induced depletion of mtDNA plays an important role in drug cytotoxicity.