The P‐Glycoprotein 170: Just a Multidrug Resistance Protein or a Protean Molecule?

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“…Among the multiple targets are certain key markers. One pathway that might link NaK and MDR is the one related to c-Myc because c-Myc is involved in regulating the expression of MDR [94] and P-gp, the product of the MDR1 gene [95]; c-Myc activates MDR-1 transcription by binding the E-box motif (CACGTG) in the MDR1 gene promoter [96]. Our data indicate that (i) CS anti-tumour efficiency is correlated with the ability to down-regulate c-Myc [97] and (ii) 19-hydroxy-2′′-oxovoruscharin impairs the expression of five Myc-related genes [90], suggesting a broad effect on the c-Myc pathway.…”

Effect of 9-cis retinoic acid and all-trans retinoic acid in combination with verapamil on P-glycoprotein expression in L1210 cells

“…With respect to cancer therapy, several lines of evidence have shown that retinoids are involved in the development of multidrug resistance (MDR) via the activation of RAR and RXR, particularly the MDR subtype that is mediated by the membrane transporter P-glycoprotein (P-gp) [16]. P-glycoprotein is a drug efflux ATPase that was classified as ABCB1 member of the ABC transporter gene family, and shows broad specificity to diverse groups of substances, including anthracyclines (e.g., doxorubicin), vinca alkaloids (e.g., vincristine -VCR), actinomycines (e.g., actinomycin D, dactinomycines), taxols (e.g., paclitaxel), alkylating agents (e.g., mytomycin C), peptide antibiotics (e.g., gramicidin, valinomycin), and many others [5,6].The transcription of P-gp is controlled by PXR and other nuclear receptors that are dimerization partners of RXR [33].…”