title: The in-vitro antiproliferative effect of PRI-2191 and imatinib applied in combined treatment with cisplatin, idarubicin, or docetaxel on human leukemia cells.
abstract: Imatinib mesylate (Gleevec, STI571) is a specific inhibitor of the Bcr/Abl fusion tyrosine kinase that exhibits potent antileukemic effects in chronic myelogenous leukemia. Bcr/Abl-positive K562 and Bcr/Abl-negative HL-60 human leukemia cells were used to investigate the effect of PRI-2191, a calcitriol analog, on the biological effects of imatinib combined with other anticancer drugs. The results show that PRI-2191 enhances the antiproliferative effect of imatinib on HL-60 cells. When these two agents together are applied with either docetaxel or cisplatin, but not with idarubicin, the antiproliferative effect could still be enhanced. Moreover, when the interaction between the chemotherapy agents was antagonistic or additive, PRI-2191 could even shift it to synergism. This effect correlated with an accumulation of HL-60 cells in the G0/G1 phase of the cell cycle and a decrease in the percentage of cells in the G2/M and S stage in the ternary combinations used. PRI-2191 did not influence apoptosis induced by imatinib alone or in ternary combinations with all the chemotherapy agents used. These results may suggest that the stronger antiproliferative effect of the combined treatment with PRI-2191 on HL-60 cells is related to cell cycle arrest rather than to the induction of apoptosis.
authors.affiliation: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Wrocław, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Switalska
authors.forename: Anna
authors.initials: A
authors.lastname: Nasulewicz-Goldeman
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Opolska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Maciejewska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kutner
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D004100:Dihydroxycholecalciferols / Q000008:administration & dosage / Q000494:pharmacology*; D000077143:Docetaxel; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D000068877:Imatinib Mesylate; D020014:K562 Cells / Q000187:drug effects; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D001549:Benzamides; D004100:Dihydroxycholecalciferols; D010879:Piperazines; D011743:Pyrimidines; D043823:Taxoids; D000077143:Docetaxel; C023850:1 alpha,24-dihydroxyvitamin D3; D000068877:Imatinib Mesylate; D002945:Cisplatin; D015255:Idarubicin