The antiproliferative alkylphospholipid S-1-O-phosphocholine-2-N-acetyl-octadecane induces apoptosis in leukemia cell lines.
Lipids are involved in a multitude of important cellular functions. They act as signaling molecules and can even provoke apoptosis. In this context we investigated the efficacy of synthetic alkylphosphocholines (APCs) as potential anti-cancer membrane-affecting drugs. Leading to novel therapeutic strategies for cancer treatment, the new agents interact with the cell membrane and do not affect the DNA. The data presented here show a cell death-inducing capacity for 1-O-phosphocholine-2[S]-O-acetyl-octadecane and 1-O-phosphocholin-2[S]-N-acetyl-octadecane in Jurkat T cells as well as in BJAB cells. The activation of caspases is generally required for the induction of apoptosis as shown by experiments with specific caspase inhibitors. The results point on the one hand to the formation of a functional DISC after APC-treatment as indicated by the clustering of receptor molecules and on the other hand to the dependency on the instrinsic apoptotic machinery and the downstream of mitochondria-activated apoptosome.
Krug
H F
HF
Forschungszentrum Karlsruhe GmbH, Institute of Toxicology and Genetics, 76021 Karlsruhe, Germany. krug@itg.fzk.de
Oberle
C
C
Matzke
A
A
Massing
U
U
D000478:Alkylation; D061945:Caspase Inhibitors; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia; D010713:Phosphatidylcholines / Q000494:pharmacology*
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D010713:Phosphatidylcholines