Changes in biophysical parameters of plasma membranes influence cisplatin resistance of sensitive and resistant epidermal carcinoma cells

Exp Cell Res. 2004 Feb 15;293(2):283-91. doi: 10.1016/j.yexcr.2003.10.012.

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.

MeSH terms

  • Carcinoma / drug therapy*
  • Carcinoma / metabolism
  • Carcinoma / physiopathology
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Line, Tumor
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism
  • Cisplatin / pharmacology*
  • Clone Cells
  • Cyclic N-Oxides
  • Drug Resistance, Neoplasm / genetics*
  • Fatty Acids / metabolism
  • Fatty Acids / pharmacology
  • HeLa Cells
  • Humans
  • Isoxazoles
  • Membrane Fluidity / drug effects
  • Membrane Fluidity / genetics*
  • Membrane Lipids / metabolism
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Membrane Proteins / drug effects
  • Membrane Proteins / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / physiopathology
  • Potassium Channels / metabolism
  • Pyrimidinones

Substances

  • Cyclic N-Oxides
  • Fatty Acids
  • Isoxazoles
  • Membrane Lipids
  • Membrane Proteins
  • Potassium Channels
  • Pyrimidinones
  • oxonol dyes (isoxazole)
  • 5-doxylstearic acid
  • merocyanine dye
  • Cisplatin
  • margaric acid