title: Effects of digoxin on cell cycle, apoptosis and NF-κB pathway in Burkitt's lymphoma cells and animal model.
abstract: Digoxin has potential antitumor properties. This study investigated whether digoxin suppressed Burkitt's lymphoma (BL) cells. Raji and NAMALWA cells were exposed to digoxin, followed by assay of cell viability, apoptosis and cell cycle. Western blotting was used to analyze NF-κB activity. A xenograft model was established for therapeutic efficacy evaluation. Digoxin inhibited cell growth and resulted in apoptosis and cell cycle arrest (G0/G1 for Raji cells; G2/M for NAMALWA cells). Digoxin inhibited DNA synthesis and induced morphological apoptotic characteristics. Besides, digoxin inhibited NF-κB and TNF-α-stimulated NF-κB activity, and suppressed NF-κB initiating genes (Bcl-2, Bcl-xL, cyclin D1, and c-myc), however, increased p21cip1. Digoxin activated caspase-9/3. Furthermore, digoxin inhibited xenograft tumors growth and reduced Ki-67 and c-myc. Digoxin exerted antitumor effects on BL cells in vitro and in vivo might through regulating NF-κB and caspase pathway. These outcomes highlight the potential of digoxin as a therapeutic agent for BL.
authors.affiliation: a Department of Hematology , Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School , Nanjing , PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: a Department of Hematology , Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School , Nanjing , PR China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Xu
authors.affiliation: a Department of Hematology , Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School , Nanjing , PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: a Department of Hematology , Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School , Nanjing , PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhou
authors.affiliation: b Department of Hematology , Nanjing Drum Tower Hospital, Clinical College of Medical College of Southeast University , Nanjing , PR China.
authors.forename: Ruju
authors.initials: R
authors.lastname: Wang
authors.affiliation: c Department of Maternity Intensive Care Unit , Nanjing Maternity and Child Health Hospital Affiliated to Nanjing Medical University , Nanjing , PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Meng
authors.affiliation: a Department of Hematology , Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School , Nanjing , PR China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: a Department of Hematology , Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School , Nanjing , PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: a Department of Hematology , Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School , Nanjing , PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: a Department of Hematology , Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School , Nanjing , PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ouyang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004077:Digoxin / Q000494:pharmacology*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D004077:Digoxin; D053148:Caspase 3; D053453:Caspase 9
keywords: Burkitt’s lymphoma; Digoxin; NF-κB; apoptosis; caspase; cell cycle arrest