Trichostatin A induces apoptotic cell death of HeLa cells in a Bcl-2 and oxidative stress-dependent manner

Trichostatin A (TSA) as a HDAC inhibitor can regulate many biological properties including apoptosis and cell proliferation in various cancer cells. Here, we evaluated the effect of TSA on the growth and death of He La cervical cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. Dose- and time-dependent growth inhibition was observed in He La cells with an IC50, of approximately 20 nM at 72 h. This agent also induced apoptotic cell death, as evidenced by annexin V-FITC staining cells, caspase-3 activation and the loss of mitochondrial membrane potential (MMP; Delta Psi(m)). In addition, the administration of Bcl-2 siRNA intensified TSA-induced He La cell death. All of the tested caspase inhibitors significantly rescued some cells from TSA-induced He La cell death. TSA increased O-2(center dot-) level and induced GSH depletion in He La cells. Caspase inhibitors significantly attenuated O-2(center dot-) level and GSH depletion in TSA-treated He La cells. In addition, N-acetyl cysteine (NAC; a well known antioxidant) significantly prevented cell death and GSH depletion in TSA-treated He La cells via decreasing O-2(center dot-) level. In conclusion, TSA inhibited the growth of HeLa cells via Bcl-2-mediated apoptosis, which was closely related to O-2(center dot-) and GSH content levels.