title: Tetraarsenic hexoxide demonstrates anticancer activity at least in part through suppression of NF-κB activity in SW620 human colon cancer cells.
abstract: Tetraarsenic hexoxide (As4O6) has been used in Korean traditional medicine for the treatment of cancer since the late 1980's, and arsenic trioxide (As2O3) is currently used as a chemotherapeutic agent. Previous studies suggest that the As4O6-induced cell death pathway is different from that of As2O3 and its mechanism of anticancer activity remains unclear. Nuclear factor (NF)-κB is a well-known transcription factor involved in cell proliferation, invasion and metastasis. Hence, in the present study, we investigated the effects of As4O6 on NF-κB activity and NF-κB-regulated gene expression in vitro and in vivo. The cytotoxicity assay revealed that As4O6 inhibited the growth of SW620 cells in a dose-dependent manner, and the half maximal inhibitory concentration (IC50) was ~1 µM after a 48 h treatment. As4O6 suppressed NF-κB activation and suppressed inhibitory κBα (IκBα) phosphorylation stimulated by tumor necrosis factor (TNF). As4O6 also suppressed downstream NF-κB-regulated proteins involved in cancer anti-apoptosis, proliferation, invasion and metastasis. In addition, As4O6 marginally suppressed tumor growth and the anti-NF-κB activity was confirmed using an in vivo xenograft mouse model in which animals were injected with SW620 cells. The present study provides evidence that As4O6 has anticancer properties through suppression of NF-κB activity and NF-κB-mediated cellular responses.
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Won Sup
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Yun
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Arulkumar
authors.initials: A
authors.lastname: Nagappan
authors.affiliation: School of Veterinary and Research Institute of Life Science, Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Jing Nan
authors.initials: JN
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Surgery, Konkuk University School of Medicine, Seoul 143-701, Republic of Korea.
authors.forename: Seong-Hwan
authors.initials: SH
authors.lastname: Chang
authors.affiliation: Department of Pathology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Dong Chul
authors.initials: DC
authors.lastname: Kim
authors.affiliation: Department of Pathology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Jeong-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Jin-Myung
authors.initials: JM
authors.lastname: Jung
authors.affiliation: Department of Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Soon Chan
authors.initials: SC
authors.lastname: Hong
authors.affiliation: Department of Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Woo Song
authors.initials: WS
authors.lastname: Ha
authors.affiliation: School of Veterinary and Research Institute of Life Science, Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Gonsup
authors.initials: G
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051550:I-kappa B Kinase / Q000096:biosynthesis; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D010087:Oxides / Q000008:administration & dosage*; D010766:Phosphorylation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D016328:NF-kappa B; D010087:Oxides; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase; D000077237:Arsenic Trioxide