Erufosine, a novel alkylphosphocholine, induces apoptosis in CLL through a caspase-dependent pathway

Leuk Res. 2010 Aug;34(8):1064-9. doi: 10.1016/j.leukres.2009.12.003. Epub 2010 Jan 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Caspases / metabolism*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Organophosphates / pharmacology*
  • Phospholipases A2 / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quaternary Ammonium Compounds / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Organophosphates
  • Quaternary Ammonium Compounds
  • erucylphospho-N,N,N-trimethylpropylammonium
  • Proto-Oncogene Proteins c-akt
  • Phospholipases A2
  • Caspases