Increased accumulation of drugs in a multidrug resistant cell line by alteration of membrane biophysical properties

Biochim Biophys Acta. 1993 Feb 17;1175(3):277-82. doi: 10.1016/0167-4889(93)90217-d.

Abstract

Growth of CHRC5 multidrug resistant cells in media enriched in a saturated C-17 fatty acid, heptadecanoic acid, resulted in these cells accumulating vinblastine at a rate and to an extent comparable to that of the parental cell line AB1. The fatty acid-enriched growth media had no effect on the ability of AB1 cells to take up vinblastine. The action of amphiphiles on the uptake of rhodamine dyes by CHRC5 cells was compared with the increased dye accumulation affected by verapamil. Membrane rigidifying agents, such as the saturated fatty acid stearic acid, or the cholesterol derivatives, cholesteryl hemisuccinate and cholesteryl phosphorylcholine, as well as a membrane fluidizing unsaturated fatty acid, linoleic acid, could significantly increase dye uptake, although not as well as verapamil. These results taken in conjunction with other reports in the literature, demonstrate that multidrug resistance is sensitive to alterations of membrane properties. They suggest that perturbation of the membrane to either increased or to decreased membrane fluidity can lower the level of resistance.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line / drug effects
  • Cell Line / metabolism
  • Cell Membrane / chemistry
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Cell Membrane Permeability / drug effects
  • Cholesterol Esters / pharmacology
  • Colchicine / metabolism
  • Cricetinae
  • Cricetulus
  • Drug Resistance
  • Fatty Acids / analysis
  • Fatty Acids / pharmacology
  • Linoleic Acid
  • Linoleic Acids / pharmacology
  • Membrane Fluidity / drug effects
  • Pharmaceutical Preparations / metabolism*
  • Rhodamines / metabolism
  • Stearic Acids / pharmacology
  • Vinblastine / metabolism

Substances

  • Cholesterol Esters
  • Fatty Acids
  • Linoleic Acids
  • Pharmaceutical Preparations
  • Rhodamines
  • Stearic Acids
  • stearic acid
  • Vinblastine
  • Linoleic Acid
  • Colchicine
  • cholesteryl succinate
  • margaric acid