title: 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.
  
  
  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.
authors.affiliation: Menarini Ricerche S.p.A., Via Tito Speri 10, 00040 Pomezia, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bressan
authors.forename: Federica
authors.initials: F
authors.lastname: Nardelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Bellarosa
authors.forename: Mario
authors.initials: M
authors.lastname: Bigioni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curcurù
authors.forename: Barbara
authors.initials: B
authors.lastname: Curatella
authors.forename: Attilio
authors.initials: A
authors.lastname: Crea
authors.forename: Carlo Alberto
authors.initials: CA
authors.lastname: Maggi
authors.forename: Stefano
authors.initials: S
authors.lastname: Manzini
authors.forename: Monica
authors.initials: M
authors.lastname: Binaschi
mesh_terms: 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
chemical_list: D000903:Antibiotics, Antineoplastic; D004272:DNA, Mitochondrial; D004187:Disaccharides; D004317:Doxorubicin; C107602:sabarubicin