title: The rare-earth yttrium complex [YR(mtbmp)(thf)] triggers apoptosis via the extrinsic pathway and overcomes multiple drug resistance in leukemic cells.
abstract: A major problem in treating patients with acute lymphoblastic leukemia is the development of drug resistance. In the current study, we investigated the anticancer properties of the novel rare-earth yttrium complex [YR(mtbmp)(thf)] in various established cell lines, and moreover, we identified the involved apoptotic pathway. Further aim was to investigate whether synergistic effects could be reached in combination with the conventional drug vincristine. We used the yttrium complex [YR(mtbmp)(thf)] in cells of leukemia (Nalm-6) and lymphoma (BJAB) and identified the main mechanism of the apoptosis induction by measuring the amount of hypodiploid DNA via FACS Scan analysis. Exposure of BJAB cells to [YR(mtbmp)(thf)] led to a death receptor-mediated reduction of cell viability and induction of apoptosis. The independence of Bcl-2 expression supports the suggestion that the [YR(mtbmp)(thf)]-induced apoptosis is mainly mediated via the extrinsic pathway. The extensive anti-tumor activity of [YR(mtbmp)(thf)] could be underlined by its capability to overcome multiple drug resistance in leukemic cells (Nalm-6) that are characterized by an overexpression of P-glycoprotein. [YR(mtbmp)(thf)] in combination with the conventional drug vincristine displayed impressive synergistic effects. We demonstrate in vitro efficiency of [YR(mtbmp)(thf)] in cells of hematological malignancies and reveal its ability to be a possible agent for polychemotherapy.
authors.affiliation: Department of Pediatric Oncology/Hematology, University Medical Center Charité Berlin, 13353 Berlin, Germany. soo-young.lee@charite.de
authors.forename: Soo-Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Ilja
authors.initials: I
authors.lastname: Peckermann
authors.forename: Elise
authors.initials: E
authors.lastname: Abinet
authors.forename: Jun
authors.initials: J
authors.lastname: Okuda
authors.forename: Günter
authors.initials: G
authors.lastname: Henze
authors.forename: Aram
authors.initials: A
authors.lastname: Prokop
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000494:pharmacology*; D053938:DNA Fragmentation; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D014162:Transfection; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D014750:Vincristine