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Cholesterol increases in a nonlinear way with the level of chemoresistance of the human CEM acute lymphoblastic leukemia and the membrane cholesterol can modulate the P-glycoprotein ATPase activity. The analysis highlights the complex effect of cholesterol on the multidrug resistance (MDR) phenotype and also the possibility of chemosensitizing resistant cells by the modulation of their membrane cholesterol content.

A study was conducted to analyze the overexpression and purification of the C-terminal nucleotide-binding domain of a parasite Pgp-like multidrug transporter that is encoded by the ltrmdr I of Leishmania tropica. Direction interaction with various classes of flavonoids and reversal of the multidrug resistance was also examined. Results indicated that flavonoids that bind with high affinity to the cytosolic domain of the transporter increases daunomycin accumulation in a L. tropica line overexpressing the transporter.

Experiment was conducted to prove the hypothesis that a longer 371-705 domain, including tryptophan-696 as an intrinsic probe, which bound MANT-ATP with identical affinity, also interacts with steroids that have been proven to modulate anticancer drug efflux from P-glycoprotein-positive multidrug-resistant cells. Results prove that both ATP and steroid-binding regions are present on the cytosolic extended-NBD1 domain of P-glycoprotein which constitutes a promising tool for the identification of amino acids involved in both types of binding.