Sabarubicin (MEN10755)-induced Apoptosis is Independent from mtDNA in A2780 Human Ovarian Tumor Cells

Abstract

Background: The role of mitochondrial DNA (mtDNA) in anthracycline-induced apoptosis is controversial. Sabarubicin accumulates in the mitochondria of A2780 human ovarian tumor cells. The effects of this new anthracycline on the structure and the functionality of mtDNA, as well as on the apoptosis of mtDNA-depleted cells have been investigated. Materials and Methods: Sabarubicin-induced mtDNA cleavage was detected by Southern blotting and mitochondrial mRNA expression was analyzed by real-time PCR. Apoptosis was studied in mtDNA-depleted (ϱ⁰) and parental (ϱ⁺) A2780 cells detecting nuclear DNA fragmentation using ELISA and cytofluorimetrically using Annexin V/PI staining. Mitochondrial membrane potential was studied using the cyanine dye JC-1. Results: Sabarubicin induced mtDNA cleavage in the A2780 cells, but this damage did not affect mitochondrial mRNA expression. Apoptosis was induced by sabarubicin in ϱ⁰ as well as in ϱ⁺ cells. Conclusion: The results showed that mtDNA did not influence anthracycline-induced apoptosis in A2780 cells.