Dequalinium induces a selective depletion of mitochondrial DNA from HeLa human cervical carcinoma cells.
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 cytochrome c oxidase 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.
Schneider Berlin
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KR
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida, 32610-0267, USA.
Ammini
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Rowe
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TC
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D004272:DNA, Mitochondrial / Q000096:biosynthesis / Q000187:drug effects*; D003868:Dequalinium / Q000737:chemistry / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006131:Growth Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D019384:Nucleic Acid Synthesis Inhibitors / Q000737:chemistry / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms
D000970:Antineoplastic Agents; D003470:Culture Media; D004272:DNA, Mitochondrial; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D003868:Dequalinium; D003576:Electron Transport Complex IV