title: Erufosine, a novel alkylphosphocholine, induces apoptosis in CLL through a caspase-dependent pathway.
abstract: 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.
authors.affiliation: Clinic I of Internal Medicine, University of Cologne, Cologne, Germany.
authors.forename: Sonja Katharina
authors.initials: SK
authors.lastname: Königs
authors.forename: Christian Philipp
authors.initials: CP
authors.lastname: Pallasch
authors.forename: Lars Hartwin
authors.initials: LH
authors.lastname: Lindner
authors.forename: Janine
authors.initials: J
authors.lastname: Schwamb
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schulz
authors.forename: Reinhild
authors.initials: R
authors.lastname: Brinker
authors.forename: Julia
authors.initials: J
authors.lastname: Claasen
authors.forename: Aditya
authors.initials: A
authors.lastname: Veldurthy
authors.forename: Hansjoerg
authors.initials: H
authors.lastname: Eibl
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.forename: Clemens-Martin
authors.initials: CM
authors.lastname: Wendtner
mesh_terms: 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
chemical_list: D010755:Organophosphates; D000644:Quaternary Ammonium Compounds; C472787:erucylphospho-N,N,N-trimethylpropylammonium; D051057:Proto-Oncogene Proteins c-akt; D054467:Phospholipases A2; D020169:Caspases