title: Ku70 is essential for histone deacetylase inhibitor trichostatin A-induced apoptosis.
abstract: It was previously reported that the histone deacetylase inhibitor (HDACI) trichostatin A (TSA) induced B cell lymphoma 2 (Bcl-2)-associated X protein (Bax)-dependent apoptosis in colorectal cancer (CRC) cells. In addition, Ku70 has been identified as a regulator of apoptosis, the mechanism of which proceeds via interacting with Bax. The aim of the present study was to investigate the role of Ku70 in TSA-induced apoptosis in the CRC cell lines HCT116 and HT29. The results showed that TSA induced the acetylation of Ku70, which was found to be associated with increased apoptosis. In addition, TSA treatment promoted the release of Bax from its complex with Ku70. Bax was then detected to have translocated from the cytoplasm into the mitochondria, while cytochrome c was detected to have translocated from the mitochondria into the cytoplasm. Furthermore, knockdown of Ku70 using small interfering RNA decreased TSA-induced apoptosis as well as downregulated the expression of Bax. These effects were rescued through pre-treatment of cells with the proteasome inhibitor MG132. In conclusion, the results of the present study suggested that Ku70 acetylation mediated TSA-induced apoptosis in CRC cells. In addition, Ku70 was found to be indispensable in TSA-induced apoptosis due to its role in protecting Bax from proteosomal degradation.
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of The State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Meng
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of The State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of The State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Xu-Tao
authors.initials: XT
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of The State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Li
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of The State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fan
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of The State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: He-Long
authors.initials: HL
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of The State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Qi-Bing
authors.initials: QB
authors.lastname: Mei
mesh_terms: D000107:Acetylation; D034961:Antigens, Nuclear / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D019073:HT29 Cells; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage; D000072200:Ku Autoantigen; D007976:Leupeptins / Q000008:administration & dosage; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007976:Leupeptins; D051028:bcl-2-Associated X Protein; C012589:trichostatin A; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde