Changes in biophysical parameters of plasma membranes influence cisplatin resistance of sensitive and resistant epidermal carcinoma cells |
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Authors: | Liang Xing-Jie Yin Jun-Jie Zhou Jien-Wei Wang Paul C Taylor Barbara Cardarelli Carol Kozar Michael Forte Raynard Aszalos Adorjan Gottesman Michael M |
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Institution: | Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Room 1A-09, 37 Convent Drive, Bethesda, MD 20892-4254, USA. |
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Abstract: | The mechanism of resistance of cancer cells to the anticancer drug cisplatin is not fully understood. Using cisplatin-sensitive KB-3-1 and -resistant KCP-20 cells, we found that the resistant cells have higher membrane potential, as determined by membrane potential sensing oxonol dye. Electron spin resonance and fluorescence polarization studies revealed that the resistant cells have more "fluid" plasma membranes than the sensitive cells. Because of this observed difference in membrane "fluidity," we attempted modification of the plasma membrane fluidity by the incorporation of heptadecanoic acid into KB-3-1 and KCP-20 cell membranes. We found that such treatment resulted in increased heptadecanoic acid content and increased fluidity in the plasma membranes of both cell types, and also resulted in increased cisplatin resistance in the KCP-20 cells. This finding is in accord with our results, which showed that the cisplatin-resistant KCP-20 cells have more fluid membranes than the cisplatin-sensitive KB-3-1 cells. It remains to be determined whether the observed differences in biophysical status and/or fatty acid composition alone, or the secondary effect of these differences on the structure or function of some transmembrane protein(s), is the reason for increased cisplatin resistance. |
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Keywords: | Cisplatin resistance Heptadecanoic acid Plasma membrane fluidity Membrane potential Fluorescence polarization Human epidermal carcinoma KB cells |
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