title: Combined stimulation with interferon alpha and retinoic acid synergistically inhibits proliferation of the glioblastoma cell line GB12.
abstract: Since malignant glioma displays moderate resistance to conventional therapy, a new treatment modality is needed to improve the outcome of patients with these tumors. In this study, we examined whether combination stimulation with interferon alpha (IFN-alpha) and retinoic acid (RA) affected proliferation of the glioblastoma cell line GB 12 in vitro. Stimulation with IFN-alpha alone inhibited the GB 12 cell proliferation in a dose/time-dependent fashion, as assessed by WST-1 assay and uptake of 3H-thymidine, while RA limited it only slightly. The anti-proliferative action of IFN-alpha against glioblastoma cells was enhanced by the addition of RA. The IFN-alpha/RA combination also induced apoptosis in a substantial portion of the cells, compared with either reagent alone. Bcl-2 family proteins, regulating apoptosis, were altered by these stimuli: Bcl-2 was down-regulated, while Bax-alpha was up-regulated, especially by the combination. These findings suggest that the IFN-alpha/RA combination would synergistically affect glioblastoma cell growth, probably through apoptosis induction as well as a decreased cellular DNA synthesis.
authors.affiliation: Department of Immunology and Intractable Diseases, Research Center, Tokyo Medical University, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Ohno
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Nishi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kojima
authors.forename: Jo
authors.initials: J
authors.lastname: Haraoka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Junichiro
authors.initials: J
authors.lastname: Mizuguchi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013936:Thymidine / Q000378:metabolism; D014212:Tretinoin / Q000008:administration & dosage*; D014316:Tritium; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D016898:Interferon-alpha; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D014316:Tritium; D014212:Tretinoin; D013936:Thymidine