Phorbol ester selectively stimulates the phospholipase D-mediated hydrolysis of phosphatidylethanolamine in multidrug-resistant MCF-7 human breast carcinoma cells

• Published in: Biochemical journal 1994-09, Vol.302 (3), p.649-654
• Main Authors: KISS, Z, TOMONO, M, ANDERSON, W. B
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Breast Neoplasms - metabolism; Drug Resistance, Multiple; Glycerophospholipids; Glycerylphosphorylcholine - biosynthesis; Gynecology. Andrology. Obstetrics; Humans; Hydrogen Peroxide - pharmacology; Hydrolysis - drug effects; Mammary gland diseases; Medical sciences; Phosphatidic Acids - biosynthesis; Phosphatidylcholines - metabolism; Phosphatidylethanolamines - biosynthesis; Phosphatidylethanolamines - metabolism; Phospholipase D - metabolism; Sphingosine - pharmacology; Tetradecanoylphorbol Acetate - pharmacology; Tumor Cells, Cultured; Tumors
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj3020649

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.