Fluorescence lifetime imaging insight into the effects of Taxol on cell metabolism.

Abstract

Mitochondria and microtubules are two of the main targets for many anticancer drugs, which has prompted us to investigate immediate effects of these classes of chemotherapeutic agents on the mitochondrial respiratory chain and enzyme-bound metabolic co-factors flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NADH). Cancer cells depend on NADH availability for biogenesis and to protect them from reactive oxygen species (ROS) generated from cancer cell metabolism. Microtubule integrity, besides having key importance in cell division, also has a role in mitochondrial localization and regulation. Herein, we investigate the multiple effects of Taxol on the oxygenation level, optical redox ratio (oxidative phosphorylation vs. glycolytic) and ROS-induced carbonylation in the PC-3 human prostate cancer cell line. Inhibitors rotenone/antimycin and uncoupler 2,4-dinitrophenol (DNP) are also used to investigate the effects of oxygen consumption on the metabolic outcomes.