Background:
Increased cancer survivorship represents a remarkable achievement for modern medicine. Unfortunately, though, cancer treatments have inadvertently contributed to cardiovascular damage, significantly threatening the health and quality of life of patients living with, through and beyond cancer. The wide spectrum of anti-cancer drugs and the range of their cardiovascular (CV) side effects make clinical detection of cardiotoxicity challenging without targeted and individualized approaches to monitoring and risk management. To date, the cardiotoxicity profiles of most of these drugs are still poorly understood. In this study, we aim to investigate the effects of chemotherapies directly on cardiomyocyte viability.
Method:
Primary human cardiomyocyte (HCM) cell line isolated from the ventricles of the adult heart were purchased from PromoCell (Banksia Scientific Company, Bulimba, QLD, Australia) and cultured as recommended by the manufacturer. Cell suspensions were then seeded into 96-well culture plates for experiments. HCMs were cultured with 1uM for 72 hours of n=35 chemotherapies. The viability of HCMs was determined using CellTitre-GloÒ. The experiments were repeated at least three times for each drug with HCMs of different passages.
Results:
We screened 35 various chemotherapies. We identified a total of n=15 chemotherapies that induced a significant reduction in HCM viability. These drugs were: (1) anthracycline (daunorubicin [13.7±3.2%], epirubicin [47.6±5.3%]), (2) antimetabolite (azacitidine [67.1±2.4%]), (3) taxanes (paclitaxel [60.2±3.0%]), (4) protein kinase inhibitors (lapatinib [49.8±7.0%], ponatinib [42.4±9.0%], pemigatinib [68.1±2.3%], sorafenib tosylate [52.9±10.6%], nilotinib [64.4±4.5%], dasatinib [38.5±3.6%]), (5) proteasome inhibitors (ixazomib citrate [65.4±7.2%]), (6) non-selective histone deacetylase inhibitor (panobinostat [19.1±4.1%]), poly ADP-ribose polymerase inhibitor (olaparib [68.2±1.7%]) and (7) vinca alkaloid (vincristrine sulfate [44.6±7.4%], vinblastine sulfate [31.2±3.9%]).
Conclusion:
Our results identified that not all chemotherapies have direct cardiotoxic effects on human cardiomyocytes. Further investigations into the effects of chemotherapies on cardiovascular cells such as cardiac fibroblasts and endothelial cells should be performed to comprehensively determine the spectrum of adverse CV effects of cancer treatments.