title: Trichostatin A induces apoptotic cell death of HeLa cells in a Bcl-2             and oxidative stress-dependent manner.
abstract: 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 HeLa cervical cancer cells in relation             to reactive oxygen species (ROS) and glutathione (GSH) levels. Dose- and time-dependent             growth inhibition was observed in HeLa 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; ∆ψm). In addition, the administration of Bcl-2 siRNA intensified             TSA-induced HeLa cell death. All of the tested caspase inhibitors significantly             rescued some cells from TSA-induced HeLa cell death. TSA increased O2•- level             and induced GSH depletion in HeLa cells. Caspase inhibitors significantly attenuated             O2•- level and GSH depletion in TSA-treated HeLa cells. In addition, N-acetyl             cysteine (NAC; a well known antioxidant) significantly prevented cell death and             GSH depletion in TSA-treated HeLa cells via decreasing O2•- level. In conclusion,             TSA inhibited the growth of HeLa cells via Bcl-2-mediated apoptosis, which was             closely related to O2•- and GSH content levels.
authors.affiliation: Department of Physiology, Chonbuk National University, JeonJu, Republic of Korea.
authors.forename: Bo Ra
authors.initials: BR
authors.lastname: You
authors.forename: Woo Hyun
authors.initials: WH
authors.lastname: Park
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism*; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C012589:trichostatin A; D053148:Caspase 3; D006655:Histone Deacetylases; D005978:Glutathione; D000111:Acetylcysteine