Modulation of MCF-7 breast cancer cell signal transduction by linoleic acid and conjugated linoleic acid in culture.
The effects of modifying membrane fatty acid composition on cell growth, phospholipase C (PLC) and protein kinase C (PKC) activities, and prostaglandin E2 (PGE2) secretion were investigated. Hormone responsive MCF-7 human breast cancer cells were incubated in a serum-free medium containing epidermal growth factor and supplemented with physiologic concentrations (0.18-1.78 x 10(-5) M) of linoleic acid (LA) or conjugated linoleic acid (CLA). Linoleic acid stimulated cancer cell growth, while CLA was inhibitory. Supplementation with LA or CLA altered cell membrane composition. Linoleic acid stimulated PLC activity with or without GTP gamma (S), and tended to increase membrane PKC activity. However, CLA supplementation did not modify membrane PLC or PKC activity. Prostaglandin E2 secretion was not influenced by LA or CLA. These data show that growth inhibition by CLA was not mediated through PLC-, PKC- or PGE2-dependent signal transduction pathways, suggesting that another inhibitory mechanism may be involved. Although biological differences appeared to be modest (5-20% of control), the fact that LA and CLA treatment resulted in significant biological effects at physiologic concentrations is relevant, since most human cancers require years to develop.
Park
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Y
Department of Food Science and Human Nutrition, Washington State University, Pullman 99164-6376, USA.
Allen
K G
KG
Shultz
T D
TD
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D016895:Culture Media, Serum-Free; D003600:Cytosol / Q000201:enzymology; D015232:Dinoprostone / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D019787:Linoleic Acid / Q000494:pharmacology*; D008041:Linoleic Acids / Q000494:pharmacology*; D044243:Linoleic Acids, Conjugated; D008563:Membrane Lipids / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D016588:Anticarcinogenic Agents; D016895:Culture Media, Serum-Free; D005227:Fatty Acids; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; D008563:Membrane Lipids; C046938:9,11-linoleic acid; D004815:Epidermal Growth Factor; D019787:Linoleic Acid; D011493:Protein Kinase C; D010738:Type C Phospholipases; D015232:Dinoprostone