Erufosine, a novel alkylphosphocholine, induces apoptosis in CLL through a caspase-dependent pathway.
The alkylphosphocholine (APC) erufosine is a synthetic phospholipid analogue with antineoplastic activity. APC are known to interact with lipid metabolism and modulate cellular signaling pathways, particularly the phosphorylation of Akt. Here, in primary CLL cells induction of apoptosis was detected with an IC50 of 22muM whereas healthy donor PBMC were less sensitive towards erufosine. Treatment with erufosine caused dose-dependent cleavage of PARP, co-incubation with caspase inhibitor z-VAD almost completely abrogated the cytotoxic effect of erufosine indicating a caspase-dependent mechanism of erufosine. Erufosine was shown to induce apoptosis in primary CLL cells and merits further investigation regarding therapeutic options in CLL.
Königs
Sonja Katharina
SK
Clinic I of Internal Medicine, University of Cologne, Cologne, Germany.
Pallasch
Christian Philipp
CP
Lindner
Lars Hartwin
LH
Schwamb
Janine
J
Schulz
Alexandra
A
Brinker
Reinhild
R
Claasen
Julia
J
Veldurthy
Aditya
A
Eibl
Hansjoerg
H
Hallek
Michael
M
Wendtner
Clemens-Martin
CM
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010755:Organophosphates / Q000494:pharmacology*; D054467:Phospholipases A2 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D010755:Organophosphates; D000644:Quaternary Ammonium Compounds; C472787:erucylphospho-N,N,N-trimethylpropylammonium; D051057:Proto-Oncogene Proteins c-akt; D054467:Phospholipases A2; D020169:Caspases