title: Down-Regulation of Thioredoxin1 Is Involved in Death of Calu-6 Lung Cancer Cells Treated With Suberoyl Bishydroxamic Acid.
abstract: Suberoyl bishydroxamic acid (SBHA), a histone deacetylase (HDAC) inhibitor, can show an anticancer effect. In this study, we investigated the effects of SBHA on the growth inhibition and death of Calu-6 and NCI-H1299 cells in relation to reactive oxygen species (ROS) and antioxidant levels. SBHA inhibited the growth of Calu-6 and NCI-H1299 lung cancer cells with an IC50 of 50 µM at 72 h. This agent induced apoptosis in Calu-6 cells and triggered to a G2/M phase arrest in NCI-H1299 cells. Although it also reduced the growth of normal human pulmonary fibroblast (HPF) cells, the susceptibility of Calu-6 cells to SBHA was higher than that of HPF cells. In addition, SBHA did not affect the growth of human small airway epithelial cells (HSAEC). Regarding ROS and antioxidant levels, SBHA increased ROS level and glutathione (GSH) depletion in Calu-6 and NCI-H1299 cells whereas it decreased ROS levels in HPF and HSAEC. SBHA also decreased thioredoxin1 (Trx1) level in Calu-6 cells. Although the down-regulation of Trx1 intensified apoptosis and ROS level in SBHA-treated Calu-6 cells, the overexpression of Trx1 attenuated apoptosis and ROS level in these cells. This down-regulation of Trx1 did not affect apoptosis-signaling regulating kinase1 (ASK1) activation. In conclusion, the down-regulation of Trx1 by SBHA was closely involved in cell death in Calu-6 cells.
authors.affiliation: Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, JeonJu, 561-180, Republic of Korea.
authors.forename: Bo Ra
authors.initials: BR
authors.lastname: You
authors.affiliation: Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, JeonJu, 561-180, Republic of Korea.
authors.forename: Woo Hyun
authors.initials: WH
authors.lastname: Park
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008168:Lung / Q000166:cytology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006877:Hydroxamic Acids; D017382:Reactive Oxygen Species; C528828:suberoyl bis-hydroxamic acid; D013879:Thioredoxins; D005978:Glutathione
keywords: GLUTATHIONE; LUNG CANCER; REACTIVE OXYGEN SPECIES; SUBEROYL BISHYDROXAMIC ACID; THIOREDOXIN