Mesh : Animals Anthracyclines / toxicity Apoptosis Calcium-Calmodulin-Dependent Protein Kinases / metabolism Doxorubicin / toxicity Drug Resistance Free Radicals Humans JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases

来  源:   DOI:10.3892/ijmm.1.2.491   PDF(Sci-hub)

Abstract:
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.
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