Anthracycline-derived chemotherapeutics in apoptosis and free radical cytotoxicity (Review).
Anthracycline-derivatives are frequently used chemotherapeutics in treatment of numerous human malignancies. Anthracyclines are known for their complex cytotoxic mechanism involving i) inhibition of enzymes such as topoisomerase II, RNA polymerase, cytochrome c oxidase and others; ii) intercalation into DNA; iii) chelation of iron and generation of reactive oxygen species (ROS); iv) induction of apoptosis. Here, mechanistic aspects for successful cytostasis and for side effects, e.g. cardiomyopathy, are discussed. We emphasize recent developments in anthracycline-mediated apoptosis and focus on a well known representative, doxorubicin (adriamycin, adriblastin). We reflect on the role of oxidative stress and interactions with intracellular signaling pathways.
Müller
I
I
Department of Haematology and Oncology, Children's University Hospital, D-72070 Tubingen, Germany.
Niethammer
D
D
Bruchelt
G
G
D000818:Animals; D018943:Anthracyclines / Q000633:toxicity*; D017209:Apoptosis; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity; D004351:Drug Resistance; D005609:Free Radicals; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases
D018943:Anthracyclines; D005609:Free Radicals; D004317:Doxorubicin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases