Inhibition of glycosylphosphatidylinositol (GPI) phospholipase D by suramin-like compounds.
A number of proteins are found attached to the plasma membrane of mammalian cells by a glycosylphosphatidylinositol (GPI) anchor that can be cleaved by GPI specific phospholipase D (GPI-PLD). There are no known specific inhibitors of GPI-PLD. We examined some inhibitors of phosphatidylinositol specific phospholipase C (PI-PLC) for their ability to inhibit human serum and human bone marrow cell GPI-PLD. Azo analogues of suramin were found to be potent inhibitors of GPI-PLD. One compound had an IC50 of 3.7 microM that was 10-fold lower than the IC50 required to inhibit PI-PLC. The azo suramin analogues inhibited cancer cell growth at concentrations similar to those required to inhibit GPI-PLD, and below concentrations required to inhibit growth factor binding. It is possible that inhibition of cell growth might be related to the ability of the compounds to inhibit GPI-PLD.
Department of Cell Biology, New York University Medical School, New York, USA.
G
G
Brunner
L
L
Zalkow
E
E
Burgess
D B
DB
Rifkin
E L
EL
Wilson
E
E
Gruszecka-Kowalik
G
G
Powis
D002455:Cell Division / Q000187:drug effects; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D010739:Phospholipase D / Q000037:antagonists & inhibitors*; D013498:Suramin / Q000031:analogs & derivatives / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D013498:Suramin; D010739:Phospholipase D; C065017:glycoprotein phospholipase D