title: Anthracyclines and mitochondria.
abstract: Anthracyclines remain the cornerstone in the treatment of many malignancies including lymphomas, leukaemias, and sarcomas. Unfortunately, the clinical use of these potent chemotherapeutics is severely limited by the development of a progressive dose-dependent cardiomyopathy that irreversibly evolves toward congestive heart failure. The molecular mechanisms responsible for anthracycline anticancer activity as well as those underlying anthracycline-induced cardiotoxicity are incompletely understood and remain a matter of remarkable controversy. Anthracyclines have long been considered to induce cardiotoxicity by mechanisms different from those mediating their anticancer activity. In particular, anthracycline antitumor efficacy is associated with nuclear DNA intercalation, topoisomerase II inhibition and drug-DNA adducts formation, whereas the cardiotoxicity is prevalently ascribed to oxidative stress and mitochondrial dysfunction. At present, however, the view that distinct mechanisms are implied in anticancer and cardiotoxic responses to anthracycline therapy does not seem fully convincing since beneficial (anticancer) and detrimental (cardiotoxic) effects are to some extent overlapping, share the subcellular organelle targets, the molecular effectors and the pathophysiological processes (i.e. DNA strand breaks, oxidative stress, signalling pathways, mitochondrial dysfunctions, apoptosis etc.).Here, we review the potential role of mitochondria in the molecular mechanisms underlying anthracyclines anticancer activity as well as in the pathogenesis of anthracycline-induced cardiotoxicity.
authors.affiliation: Institute of Biochemistry and Clinical Biochemistry, Catholic University School of Medicine, Rome, Italy. alvaro.mordente@rm.unicatt.it
authors.forename: Alvaro
authors.initials: A
authors.lastname: Mordente
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Meucci
authors.forename: Andrea
authors.initials: A
authors.lastname: Silvestrini
authors.forename: Giuseppe Ettore
authors.initials: GE
authors.lastname: Martorana
authors.forename: Bruno
authors.initials: B
authors.lastname: Giardina
mesh_terms: D018943:Anthracyclines / Q000494:pharmacology*; D018736:DNA Adducts / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D018943:Anthracyclines; D018736:DNA Adducts