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• W2037236799 abstract "Multidrug-resistance (MDR) in cancer cells is often associated with marked changes in the membrane cholesterol levels. To assess the cholesterol-dependence of MDR modulator efficiency in terms of the drug-membrane interactions, the ability of 5 MDR-modulators to induce the leakage of Sulphan blue through anionic liposomes was quantified at various mole fractions x(chol) of cholesterol (0-0.42). Depending on the electric charge of the drug, cholesterol modified to a large extent either the permeation dose inducing 50% dye leakage (PD(50)) or the co-operativity (h) of the permeation process. The PD(50) of Triton X-100 (non-ionic) and that of diltiazem and verapamil (mono-basic amines) varied only slightly (0.3 mM) with the cholesterol level, whereas the co-operativity increased by 1.9-2.7. On the reverse, the PD(50) of a thioacridine derivative and mepacrine (di-basic amines) increased by 4.8-7.5 mM in the cholesterol range investigated, whereas the co-operativity (h) increased slightly (0.2-0.7). In the permeation process, the rate-limiting character of the electric charge (z) of the drug is likely to be strengthened by high cholesterol levels. The results provide evidence that in resistant tumours exhibiting high cholesterol levels, the MDR might be reversed by favourable drug-membrane interactions if the modulators are designed in the form of highly lipophilic mono-basic drugs that counteract the effects of cholesterol on the membrane dipolar potential and membrane fluidity." @default.
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• W2037236799 date "2003-01-01" @default.
• W2037236799 modified "2023-10-17" @default.
• W2037236799 title "Effects of cholesterol on dye leakage induced by multidrug-resistance modulators from anionic liposomes" @default.
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• W2037236799 doi "https://doi.org/10.1016/s0928-0987(02)00243-9" @default.
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