Thymosin β4 knockdown disrupts mitochondrial functions of SW480 human colon cancer cells

Thymosin beta 4 (T beta 4), overexpressed in various tumors, has been shown to be involved in cellular anti-oxidation. Reactive oxygen species (ROS) function as signaling molecules and play certain roles in tumor progression. To assess the anti-oxidative role of endogenous T beta 4 in tumor cells, its expression in SW480 cells was knocked down by a shRNA, which induced significant increases of ROS. Interestingly, some cristae-lost and several electron-dense mitochondria appeared in cells with T beta 4 knockdown that was accompanied by a marked decline of the membrane potential of these organelles. Strikingly, while the ATP and lactate levels in SW480 cells were notably elevated by T beta 4 downregulation, this treatment significantly diminished the mitochondrial DNA copy number and protein levels of several subunits of the electron transport complexes. Finally, immunofluorescent staining results suggested the presence of T beta 4 in mitochondria. To the best of our knowledge, this is the first report to demonstrate that T beta 4 knockdown can disrupt the morphology and some crucial functions of mitochondria in human colorectal carcinoma (CRC) cells. (Cancer Sci 2011; 102: 1665-1672)