Alterations in myocardial energy metabolism induced by the anti-cancer drug doxorubicin.
Doxorubicin and other anthracyclines are among the most potent chemotherapeutic drugs for the treatment of acute leukaemia, lymphomas and different types of solid tumours such as breast, liver and lung cancers. Their clinical use is, however, limited by the risk of severe cardiotoxicity, which can lead to irreversible congestive heart failure. There is increasing evidence that essential components of myocardial energy metabolism are among the highly sensitive and early targets of doxorubicin-induced damage. Here we review doxorubicin-induced detrimental changes in cardiac energetics, with an emphasis on the emerging importance of defects in energy-transferring and -signalling systems, like creatine kinase and AMP-activated protein kinase.
Tokarska-Schlattner
Malgorzata
M
Institute of Cell Biology, ETH Zurich, Hönggerberg HPM D24, CH-8093 Zürich, Switzerland. malgorzata.tokarska@cell.biol.ethz.ch
Wallimann
Theo
T
Schlattner
Uwe
U
D055372:AMP-Activated Protein Kinases; D000255:Adenosine Triphosphate / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D003402:Creatine Kinase / Q000378:metabolism; D004317:Doxorubicin / Q000009:adverse effects*; D004579:Electron Transport / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism; D009097:Multienzyme Complexes; D009206:Myocardium / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010725:Phosphocreatine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D015398:Signal Transduction
D000903:Antibiotics, Antineoplastic; D005227:Fatty Acids; D009097:Multienzyme Complexes; D010725:Phosphocreatine; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D003402:Creatine Kinase; D005947:Glucose