Dequalinium induces a selective depletion of mitochondrial DNA from HeLa human cervical carcinoma cells

Treatment of cultured human cervical carcinoma cells with the anticancer dr ug dequalinium (DEQ) was found to cause a delayed inhibition of cell. growt h. This inhibition was preceded by a loss of mitochondrial DNA (mtDNA), a d ecrease in cytochrome c oxidase activity, and an increase in the level of l actate, indicating that growth inhibition was due to the loss of mtDNA-enco ded functions, There was a progressive two-fold loss of mtDNA following eac h cell division in the presence of DEQ, suggesting that this drug was actin g by inhibiting some aspect of mtDNA synthesis. Furthermore, cells became r esistant to the growth inhibitory and cytotoxic affects of DEQ when they we re grown under conditions that bypassed the need for mtDNA-encoded function s. Resistance was not associated with significant changes in drug accumulat ion. These results suggest that the DEQ-induced depletion of mtDNA plays an important role in drug cytotoxicity. (C) 1998 Academic Press.