melphalan and Cardiotoxicity

Treatment-induced cardiotoxicity is a leading noncancer-related cause of acute and late onset morbidity and mortality in cancer patients on antineoplastic drugs such as melphalan-increasing clinical case reports have documented that it could induce cardiotoxicity including severe arrhythmias and heart failure. As the mechanism by which melphalan impairs cardiac cells remains poorly understood, here, we aimed to use cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) to investigate the cellular and molecular mechanisms of melphalan-induced cardiotoxicity.. hiPSC-CMs were generated and treated with clinically relevant doses of melphalan. To characterize melphalan-induced cardiotoxicity, cell viability and apoptosis were quantified at various treatment durations. Ca. Melphalan treatment of hiPSC-CMs induced oxidative stress, caused Ca. Melphalan induces cardiotoxicity through the oxidative stress pathway. This study provides a unique resource of the global transcriptomic and proteomic datasets for melphalan-induced cardiotoxicity and can potentially open up new clinical mechanism-based targets to prevent and treat melphalan-induced cardiotoxicity.

Topics: Cardiotoxicity; Cells, Cultured; Humans; Induced Pluripotent Stem Cells; Melphalan; Myocytes, Cardiac; Oxidative Stress; Proteomics

Topics: Antineoplastic Agents, Alkylating; Cardiotoxicity; Electrocardiography; Female; Heart Conduction System; Humans; Melphalan; Middle Aged; Multiple Myeloma; Tachycardia, Ventricular