Do Childhood Cancer Drugs Kill Heart Cells and Why
SPARC 2022 Poster Number 14
Anthracyclines are potent anti-cancer drugs used in the treatment of childhood cancers. Anthracyclines kill cancer cells by elevating levels of highly damaging molecules called reactive oxygen species (ROS) leading to a condition called oxidative stress. However, anthracyclines produce many unwanted side effects including cardiac toxicity which leads to heart failure later in life. Heart function is dependent of the billions of cells that form heart muscle. We know that anthracyclines alter the way heart cells work, but we don’t know precisely how. It may be that anthracyclines also cause unwanted ROS elevations in heart cells leading to their death. The aim of our study is to determine (1) if this is the case and (2) if anthracycline-mediated heart cell death can be prevented with antioxidants; drugs that prevent the harmful effects of ROS.
Cancer and heart cells were grown then exposed to anthracyclines with or without antioxidants. We measured oxidative stress and cell death using specialist equipment.
Anthracyclines killed cancer and heart cells. The percentage of cells killed increased as drug dose increased. Anthracyclines also increased levels of oxidative stress in both cell types. However, when antioxidants were present levels of cell death and oxidative stress were reduced.
The effects on cancer cells were expected and confirmed our methods work. However, to our knowledge this is the first study to demonstrate that anthracyclines kill heart cells via elevations of oxidative stress. Encouragingly, we also demonstrate this can be prevented. This may improve the treatment of childhood cancer saving more lives.