Activation of Calcium-Dependent Cyclosporin-Sensitive Mitochondrial Pore by Doxorubicin in Complex with Iron Ions

作者：Fedotcheva T A; Teplova V V; Fedotcheva N I^*

来源：Biologicheskie Membrany, 2018, 35(1): 79-84.

DOI：10.7868/S0233475518010097

• mitochondria
• doxorubicin
• iron ions
• calcium-induced mitochondrial pore

Doxorubicin (DOX) is an anthracycline widely used in antitumor chemotherapy of various types of cancer. However, the toxic effect of DOX extends to normal cells, causing a strong side effect on the body. The main target of the DOX in normal tissues is the mitochondria, where its toxic effect leading to a violation of mitochondrial functions may be mediated by the accumulation of iron ions. This study shows for the first time that DOX, in combination with iron ions, slows down the transport of calcium ions in rat liver mitochondria, reduces the calcium retention capacity, and activates the opening of the nonspecific mitochondrial pore, a key factor in the induction of the mitochondrial pathway of apoptosis. In the free state, which in the presence of iron ions was supported by the thiol antioxidant N-acetylcysteine or deferoxamine binding iron ions, DOX did not exert this effect on the mitochondria. We conclude that the mitochondrial toxicity of DOX is mediated by iron ions, and the formation of the DOX complex with iron ions activates the mitochondrial pathway of apoptosis and cell death.

• 出版日期2018-2