Sabarubicin (MEN10755)-induced apoptosis is independent from mtDNA in A2780 human ovarian tumor cells.
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.


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 (theta0) and parental (theta+) 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 theta0 as well as in theta+ cells.


CONCLUSIONS
The results showed that mtDNA did not influence anthracycline-induced apoptosis in A2780 cells.
Bressan
Alessandro
A
Menarini Ricerche S.p.A., Via Tito Speri 10, 00040 Pomezia, Rome, Italy.
Nardelli
Federica
F
Bellarosa
Daniela
D
Bigioni
Mario
M
Curcurù
Giuseppe
G
Curatella
Barbara
B
Crea
Attilio
A
Maggi
Carlo Alberto
CA
Manzini
Stefano
S
Binaschi
Monica
M
D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015139:Blotting, Southern; D045744:Cell Line, Tumor; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004187:Disaccharides / Q000493:pharmacokinetics / Q000494:pharmacology*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000903:Antibiotics, Antineoplastic; D004272:DNA, Mitochondrial; D004187:Disaccharides; D004317:Doxorubicin; C107602:sabarubicin