title: Inhibition of thioredoxin reductase by auranofin induces apoptosis in adriamycin-resistant human K562 chronic myeloid leukemia cells.
abstract: Mammalian thioredoxin reductase (TrxR) catalyzes the NADPH-dependent reduction of oxidized thioredoxin (Trx) and plays a central role in regulating cellular redox homeostasis, cell growth and apoptosis. Increasing evidence shows that TrxR is over-expressed or constitutively active in many tumor cells. Moreover, TrxR appears to contribute to increased tumor cell growth and a resistance to chemotherapy. In this study, we evaluated the activity of TrxR in adriamycin-resistant leukemic cells (K562/ADM) and adriamycin-sensitive parental lines (K562), and found that TrxR activity was higher in the drug resistant cell sublines K562/ADM than in K562 drug sensitive parental cells. Auranofin, a gold(I) compound clinically used as an antirheumatic agent, reduced TrxR activity and was more effective than adriamycin in decreasing cell viability in K562/ADM cells. In addition, auranofin induced apoptosis in dose-dependent manners, accompanied by caspase-3 activation in K562/ADM cells. Our results demonstrate that inhibition of TrxR and induction of apoptosis by auranofin provides its ability in overcoming adriamycin resistance in K562/ADM cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.forename: Hu-lai
authors.initials: HL
authors.lastname: Wei
authors.forename: Juan
authors.initials: J
authors.lastname: Yi
authors.forename: Huai-shun
authors.initials: HS
authors.lastname: Zhao
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Gao
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001310:Auranofin / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors; D005434:Flow Cytometry; D006801:Humans; D020014:K562 Cells; D007951:Leukemia, Myeloid / Q000473:pathology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D018501:Antirheumatic Agents; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; D001310:Auranofin; D004317:Doxorubicin; D013880:Thioredoxin-Disulfide Reductase; D053148:Caspase 3; C022616:thiazolyl blue