title: Enhanced elimination of Ph+ chromosome cells in vitro by combined hyperthermia and other drugs (AZT, IFN-alpha, TNF, and quercetin): its application to autologous bone marrow transplantation for CML.
abstract: Autologous bone marrow transplantation (ABMT) for chronic myelogenous leukemia (CML) is limited because of the difficulty in purging Ph chromosome positive cells from bone marrow cells (or peripheral blood stem cells). Combining hyperthermia with certain drugs that affect Ph+ cell growth in vivo and in vitro may enhance the killing (apoptosis) of CML cells in vitro. In this study, we chose such drugs (i.e., azidothymidine [AZT], interferon-alpha [IFN-alpha], tumor necrosis factor [TNF], and quercetin) and tested this hypothesis using two CML-derived cell lines in vitro, K562 and KU812, to enhance the killing of CML cells with heat. Our results indicate that the optimal hyperthermic purging effect is achieved by heating at 42 degrees C for 1 hour with IFN-alpha (100 U/mL) and AZT (0.5 microM/L) or with quercetin (50 microM) [corrected], depending on the sensitivity of the CML cells eliminated in vitro. K562 cells were significantly eradicated by a combination of IFN-alpha and AZT, while KU812 cells were significantly inhibited by quercetin at the temperature and drug concentrations above. This combined effect may enhance apoptosis of CML cells in vitro.
authors.affiliation: First Department of Internal Medicine, Niigata University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Osman
authors.forename: Y
authors.initials: Y
authors.lastname: Moriyama
authors.forename: A
authors.initials: A
authors.lastname: Shibata
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D016465:Bone Marrow Purging / Q000379:methods*; D016026:Bone Marrow Transplantation; D004357:Drug Synergism; D006358:Hot Temperature; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology* / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology*
chemical_list: D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha; D015215:Zidovudine; D011794:Quercetin