Phorbol ester selectively stimulates the phospholipase D-mediated hydrolysis of phosphatidylethanolamine in multidrug-resistant MCF-7 human breast carcinoma cells.
The phospholipase D (PLD)-mediated synthesis of phosphatidylethanol (PtdEtOH) and the hydrolysis of phosphatidylethanolamine (PtdEtn) and phosphatidylcholine (PtdCho) were examined in drug-sensitive and multidrug-resistant lines of MCF-7 human breast carcinoma cells. In drug-sensitive (MCF-7/WT) cells, the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) failed to enhance either the synthesis of PtdEtOH or the hydrolysis of either phospholipid. In the drug-resistant (MCF-7/MDR) cells, 100 nM PMA greatly enhanced both the synthesis of PtdEtOH (approximately 21-fold) and the hydrolysis of PtdEtn (approximately 29-fold), but had no effect on the hydrolysis of PtdCho. The PLD activators sphingosine and H2O2 were found to elicit only a slight (1.28-1.4-fold) stimulatory effect on PtdCho hydrolysis in both the MCF-7/WT and MCF-7/MDR cell types, and had only a small effect on PtdEtn hydrolysis in the MCF-7/WT cells as well. However, these agents significantly (approximately 2.6-3.5-fold) stimulated PtdEtn hydrolysis in the MCF-7/MDR cells. These data indicate that MCF-7/MDR cells contain a PtdEtn-specific PLD activity which can be selectively stimulated by PMA, sphingosine and H2O2.
Kiss
Z
Z
Hormel Institute, University of Minnesota, Austin 55912.
Tomono
M
M
Anderson
W B
WB
D001943:Breast Neoplasms / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D020404:Glycerophospholipids; D005997:Glycerylphosphorylcholine / Q000096:biosynthesis; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006868:Hydrolysis / Q000187:drug effects; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000096:biosynthesis / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism*; D013110:Sphingosine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D020404:Glycerophospholipids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C051521:phosphatidylethanol; C002449:glycerophosphoethanolamine; D005997:Glycerylphosphorylcholine; D006861:Hydrogen Peroxide; D010739:Phospholipase D; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate