Impact of Mitochondrial Targeting Antibiotics on Mitochondrial Function and Proliferation of Cancer Cells
Edward J Cochrane, James Hulit, Franz P Lagasse, Tanguy Lechertier, Brett Stevenson, Corina Tudor, Diana Trebicka, Tim Sparey, and Andrew J Ratcliffe
Some marketed antibiotics can cause mitochondria dysfunction via inhibition of the mitochondrial translation process. There is great interest in exploiting such effects within a cancer setting. To enhance accumulation of antibiotics within the mitochondria of cancer cells, and therefore delivery of a greater potency payload, a mitochondrial targeting group in the form of a triphenylphosphonium (TPP) cation was appended via an alkyl chain length consisting of 7 to 11 carbons to the ribosomal antibiotics azithromycin and doxycycline. Using MDA-MB-231 cells, the effects of each subseries on mitochondrial translation, mitochondrial bioenergetics, and cell viability are described.