title: Cyclin A and Cdk2 kinase activity are suppressed by combined treatment with tumor necrosis factor-alpha and interferon-alpha.
abstract: We previously reported that combined treatment with tumor necrosis factor-alpha (TNF-alpha) and interferon-alpha (IFN-alpha) showed a synergistic antitumor effect via regulation of cell cycle progression in the S phase. Here, we investigated the effect of the combined treatment with TNF-alpha and IFN-alpha on cell cycle regulating protein in RPMI 4788 cells. Treatment with TNF-alpha or IFN-alpha alone showed no effect on these proteins, however, the combined treatment showed suppression of cyclin A protein and its associated kinase activity. Furthermore, although the combined treatment inhibited Cdk2 kinase activity, the amount of Cdk2 protein was not affected. These results suggested that TNF-alpha and IFN-alpha work together to suppress cyclin A and Cdk2 kinase activity and to inhibit cell cycle progression in the S phase.
authors.affiliation: First Department of Surgery, Okayama University Medical School, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Satomoto
authors.forename: M
authors.initials: M
authors.lastname: Haisa
authors.forename: Y
authors.initials: Y
authors.lastname: Naomoto
authors.forename: N
authors.initials: N
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Orita
mesh_terms: D016203:CDC2 Protein Kinase / Q000378:metabolism; D042846:CDC2-CDC28 Kinases; D003110:Colonic Neoplasms / Q000473:pathology; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016213:Cyclins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D011233:Precipitin Tests; D006656:Protamine Kinase / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016213:Cyclins; D007370:Interferon Type I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D006656:Protamine Kinase; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases