In vitro effects of Taurine on Taxol-induced mitochondrial dysfunction

Mitochondria are intricately involved with essential functions in normal and cancer cells and, as such, mitochondria are a natural target for chemotherapeutic drugs. We previously showed that Taxol, even at low doses, adversely effects mitochondrial energetics, function, and intracellular migration patterns. We observed (by multiple optical means) suppression of oxidative phosphorylation (OXPHOS) and decreased adenosine triphosphate (ATP) production, increased reactive oxygen species (ROS) generation (both immediately and integrated over time), increased mitotic fraction, and the release of LDH and cytochrome <i>c</i> in Taxol-treated cells. Moreover, we observed more random (less ordered) motion of the mitochondria as well as altered mitochondrial morphology and lessened association with microtubules. Recently, several in vitro and in vivo studies have demonstrated the beneficial effects of taurine (a very abundant non-protein amino acid in most tissues, particularly in the heart, retina, brain and muscles) in maintaining mitochondrial functions. Intracellular concentrations of taurine in tissues range from 5-50 mM, but most culture conditions have little or no taurine. In this study, we show how taurine supplementation alters the impact of Taxol treatment in a variety of cell lines with varying glycolytic profiles. A549 (non-small cell lung epithelial cancer cell line), A549-<i>ρ</i> ⁰ (mitochondrial DNA-depleted derivative of A549), BEAS-2B (a non-cancer cell line derived from normal bronchial epithelium), as well as T98G (glioblastoma cell line) cells are used in this study.