Oxidative Stress and Cellular Response to Doxorubicin: A Common Factor in the Complex Milieu of Anthracycline Cardiotoxicity

The production of reactive species is a core of the redox cycling profile of anthracyclines. However, these molecular characteristics can be viewed as double-edge sword acting not only on neoplastic cells but also on multiple cellular targets throughout the body. This phenomenon translates into anthracycline cardiotoxicity that is a serious problem in the growing population of paediatric and adult cancer survivors. Therefore, better understanding of cellular processes that operate within but also go beyond cardiomyocytes is a necessary step to develop more effective tools for the prevention and treatment of progressive and often severe cardiomyopathy experienced by otherwise successfully treated oncologic patients. In this review, we focus on oxidative stress-triggered cellular events such as DNA damage, senescence and cell death implicated in anthracycline cardiovascular toxicity. The involvement of progenitor cells of cardiac and extra-cardiac origin, as well as different cardiac cell types is discussed, pointing to molecular signals that impact on cell longevity and functional competence.