Journal
CANCER CHEMOTHERAPY AND PHARMACOLOGY
Volume 62, Issue 2, Pages 321-329Publisher
SPRINGER
DOI: 10.1007/s00280-007-0612-7
Keywords
AML; alkylphosphocholine; cytarabine; cytotoxicity; interaction analysis
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Purpose 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 mu g/ml after 24 h and 3.2 mu g/ml after 72 h in HL 60 cells and 30.1 and 8.6 mu g/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.
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