Effects of anticancer drugs on the cardiac mitochondrial toxicity and their underlying mechanisms for novel cardiac protective strategies.

Mitochondria are organelles that play a pivotal role in the production of energy in cells, and vital to the maintenance of cellular homeostasis due to the regulation of many biochemical processes. The heart contains a lot of mitochondria because those muscles require a lot of energy to keep supplying blood through the circulatory system, implying that the energy generated from mitochondria is highly dependent. Thus, cardiomyocytes are sensitive to mitochondrial dysfunction and are likely to be targeted by mitochondrial toxic drugs. It has been reported that some anticancer drugs caused unwanted toxicity to mitochondria. Mitochondrial dysfunction is related to aging and the onset of many diseases, such as obesity, diabetes, cancer, cardiovascular and neurodegenerative diseases. Mitochondrial toxic mechanisms can be mainly explained concerning reactive oxygen species (ROS)/redox status, calcium homeostasis, and endoplasmic reticulum stress (ER) stress signaling. The toxic mechanisms of many anticancer drugs have been revealed, but more studying and understanding of the mechanisms of drug-induced mitochondrial toxicity is required to develop mitochondrial toxicity screening system as well as novel cardioprotective strategies for the prevention of cardiac disorders of drugs. This review focuses on the cardiac mitochondrial toxicity of commonly used anticancer drugs, i.e., doxorubicin, mitoxantrone, cisplatin, arsenic trioxide, and cyclophosphamide, and their possible chemopreventive agents that can prevent or alleviate cardiac mitochondrial toxicity.