Article

Cytotoxic activity of the third-generation bisphosphonate zoledronic acid in acute myeloid leukemia.

Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, 81377 Munich, Germany.
Leukemia Research (impact factor: 2.92). 05/2007; 31(4):531-9. DOI:10.1016/j.leukres.2006.07.013 pp.531-9
Source: PubMed

ABSTRACT The third-generation bisphosphonate zoledronic acid (ZOL) has recently been shown to be active against human tumour and leukemic cell lines. The purpose of this study was to evaluate the antileukemic potential of ZOL in acute myeloid leukemia (AML). We determined the lethal concentration 50% (LC 50) using the WST-1 assay of ZOL as being 287.9 microg/ml after 24 h and 108.3 microg/ml after 96 h in HL 60 cells and to be 382.4 and 43.2 microg/ml, respectively, in nine samples from patients with AML. The ZOL induced inhibition of proliferative activity of HL 60 cells could not be abrogated by the hematopetic growth factors G-CSF and GM-CSF. ZOL was found to by cytotoxic in HL 60 cells without activation of caspase 3. ZOL was not cross resistant with cytarabine as shown by the linear correlation of LC 50s. Both agents, however, exerted an additive cytotoxicity as revealed by isobologram-analysis and combination index. These data warrant further investigation of ZOL in the treatment of AML.

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    Article: Erufosine, a novel alkylphosphocholine, in acute myeloid leukemia: single activity and combination with other antileukemic drugs.
    Michael Fiegl, Lars H Lindner, Matthias Juergens, Hansjoerg Eibl, Wolfgang Hiddemann, Jan Braess
    [show abstract] [hide abstract]
    ABSTRACT: 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. 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. 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. Based on these data ErPC3 appears as a novel antileukemic candidate drug, which needs to be explored further in the treatment of AML.
    Cancer Chemotherapy and Pharmacology 08/2008; 62(2):321-9. · 2.83 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

active
 
acute myeloid leukemia
 
additive cytotoxicity
 
caspase 3. ZOL
 
combination index
 
data warrant
 
hematopetic growth factors G-CSF
 
HL 60 cells
 
human tumour
 
isobologram-analysis
 
lethal concentration 50%
 
linear correlation
 
patients
 
resistant
 
samples
 
third-generation bisphosphonate zoledronic acid
 
WST-1 assay
 

Michael Fiegl