Erufosine, a novel alkylphosphocholine, in acute myeloid leukemia: single activity and combination with other antileukemic drugs

Alkylphosphocholines represent a new class of cytostatic drugs with a novel mode of action. Erufosine (ErPC3), the first compound of this class that can be administered intravenously, has recently been shown to be active against human tumor and leukemic cell lines. METHODS: In order to evaluate the antileukemic potential of ErPC3 in acute myeloid leukemia (AML) the lethal concentration 50% (LC 50) was determined using WST-1 assay. For analysis of cell death, staining for Annexin V and activated caspase 3 was performed. An interaction analysis was performed by calculation of combination index and construction of isobolograms. RESULTS: The LC 50 was 7.4 microg/ml after 24 h and 3.2 microg/ml after 72 h in HL 60 cells and 30.1 and 8.6 microg/ml, respectively, in 19 fresh samples from patients with AML. ErPC3 was found to be cytotoxic in HL60 cells with distinct activation of caspase 3. ErPC3 was not cross-resistant with cytarabine, idarubicine and etoposide as shown by the linear relation of respective LC 50s. The latter agents, however, exerted an additive cytotoxicity in combination with ErPC3 as revealed by isobologram analysis and combination index, although results are uneven for idarubicine. CONCLUSION: Based on these data ErPC3 appears as a novel antileukemic candidate drug, which needs to be explored further in the treatment of AML

Effect of ether lipids on mouse granulocyte-macrophage progenitor cells.

In this study we determined the potential bone marrow toxicity of the ether lipid derivatives 1-0-octadecyl-2-0-methyl-rac-glycero-3-phosphocholine (OcMe-G-3-PC), 1-0-hexadecyl-propanediol-2-phosphocholine (He-Pr-2-PC), and hexadecylphosphocholine (He-PC). OcMe-G-3-PC inhibited the proliferation of mouse granulocytemacrophage progenitor cells (GM-CFCs) at a dose of 1 μg/ml, whereas He-Pr-2-PC and He-PC started to inhibit the growth of hemopoietic precursors at 5 μg/ml. In contrast to this finding, NMRI mice given 10 mg/kg i.v. daily for 4 weeks and 20 or 30 mg/kg for 5 days showed no bone marrow toxicity. We conclude that the dose-dependent toxic effects observed in vitro are within the physiological tolerance in vivo

Increased peripheral stem cell pool in MDS: An indication of disease progression?

Available from TIB Hannover: DtF QN1(88,49) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Characterization of membrane lectins in human colon carcinoma cells by flow cytofluorometry, drug targeting and affinity chromatography.

International audienceFlow cytofluorometry and drug targeting with labelled neoglycoproteins are used as tools to probe for membrane lectins in two human adenocarcinoma cell lines. Both cell lines express activities for galactosides, glucosides and fucosides. Affinity chromatography on gels with immobilized sugar leads to purification of an alpha-galactoside-binding protein at an apparent molecular weight of 64 kDa that also binds to lactose, maltose and fucose and exhibits Ca2+-requirement for binding, a beta-galactoside-binding protein without Ca2+-requirement at an apparent molecular weight of 14 kDa, and an alpha-glucosyl-binding protein without Ca2+-requirement at an apparent molecular weight of 34 kDa from both cell lines. The description of membrane lectins, documented here for the first human tumor cell lines, is an initial step towards a lectin-based improvement of the clinical management of human colon adenocarcinoma