Selective inhibition of phosphatidylinositol phospholipase C by cytotoxic ether lipid analogues.

摘要: Abstract The ether lipid analogue 1-octadecyl-2-methyl- rac -glycero-3-phosphocholine (ET-18-OCH 3 ) has been shown to be a direct inhibitor of Swiss 3T3 fibroblast and BG1 ovarian adenocarcinoma cell cytosolic phosphoinositide selective phospholipase C (PIPLC) using [ H]-phosphatidylinositol-(4, 5)-bisphosphate ([ H]PIP 2 as the substrate. inhibition occurred when ET-18-OCH was incorporated into substrate micelles, with 50% (IC 50 occurring at : ratio 0.04, or an assay concentration 0.4 µm, added directly incubation, IC 9.6 µm. Lipid prepared from cells exposed cytotoxic concentrations for 18 h also inhibited PIPLC O -alkyl-2-hydroxy- sn but grown 5 µm 1- did not inhibit PIPLC. cells, which were more sensitive than fibroblasts growth by , had activity one-third that cells. NIH exhibited same sensitivity similar level v- sis relatively resistant (>3-fold) twice wild type weak inhibitor, >100 D in membranes. In intact phosphatidylcholine-selective activity. results show analogues are inhibitors may related inhibitory analogues.