ANTHRACYCLINE-DERIVED CHEMOTHERAPEUTICS IN APOPTOSIS AND FREE-RADICALCYTOTOXICITY (REVIEW)

Anthracycline-derivatives are frequently used chemotherapeutics in tre atment of numerous human malignancies. Anthracyclines are known for th eir complex cytotoxic mechanism involving i) inhibition of enzymes suc h 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, mech anistic aspects for successful cytostasis and for side effects, e.g. c ardiomyopathy, are discussed. We emphasize recent developments in anth racycline-mediated apoptosis and focus on a well known representative, doxorubicin (adriamycin, adriblastin). We reflect on the role of oxid ative stress and interactions with intracellular signaling pathways.