Anthracyclines (ANTs) continue to play an irreplaceable role in oncology treatment. However, the clinical application of ANTs has been limited. In the first place, ANTs can cause dose-dependent cardiotoxicity such as arrhythmia, cardiomyopathy, and congestive heart failure. In the second place, the development of multidrug resistance (MDR) leads to their chemotherapeutic failure. Oncology cardiologists are urgently searching for agents that can both protect the heart and reverse MDR without compromising the antitumor effects of ANTs. Based on in vivo and in vitro data, we found that natural compounds, including saponins, may be active agents for other both natural and chemical compounds in the inhibition of anthracycline-induced cardiotoxicity (AIC) and the reversal of MDR. In this review, we summarize the work of previous researchers, describe the mechanisms of AIC and MDR, and focus on revealing the pharmacological effects and potential molecular targets of saponins and their derivatives in the inhibition of AIC and the reversal of MDR, aiming to encourage future research and clinical trials.

Anthracyclines (ANTs) were first identified in the 1950 s and are a landmark in the history of oncology science. ANTs, such as doxorubicin (DOX), epirubicin, daunorubicin, aclacinomycin, and valrubicin, have been extensively used in the treatment of hematologic and solid tumors, including breast cancer, leukemia, lymphoma, and sarcoma. However, the clinical application of ANTs is severely limited from two aspects. First, it triggers diverse adverse toxicities, the most serious of which is cardiotoxicity, such as arrhythmias, cardiomyopathy, and congestive heart failure. Second, long-term use of ANTs can cause tumor cells to develop multidrug resistance and then lead to chemotherapy failure. A study that followed 2625 patients treated with ANTs showed that 98% of the patients developed cardiotoxicity (defined as a > 10% reduction in left ventricular ejection fraction from baseline levels and less than 50%  in the first year. In addition, MDR is the cause of mortality in more than 90% of patients with advanced cancer.

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Mishita
Jornal co-ordinator
Journal of Heart and Cardiovascular Research