Peroxisome Proliferator-Activated Receptors in Regulation of Cytochromes P450: New Way to Overcome Multidrug Resistance?

Table 1

Summary of mechanisms of MDR [5, 6].

Mechanism of MDR	Description
Uptake transport of drug	Decreased expression of uptake transporters (reduced-folate transporters) and alternation in lipid metabolism modifying biophysical properties of the lipid bilayer influence drug uptake
Activation of detoxifying enzymes	Inactivation of drug by phase I and phase II enzymes
Drug sequestration	Drug can be trapped in subcellular organelles such as lysosomes and endosomes and then extruded from the cell
Avoiding to drug induced apoptosis	Occurs mostly via mitochondrial pathway; disruption of balance between pro-/antiapoptotic factors leads to survival of cancer cells
Enhanced DNA reparation	Cells with damaged DNA avoid to senescence, apoptosis, or necrosis
Overexpression of membrane transporters	Enhanced drug efflux by ABC transporters
Alternation in target molecules	DNA metylation, mutation of topoisomerases I and II
Microenvironment	Ph, hypoxia, population of quiescent cells
Altered signaling pathways	Block of apoptosis and expression of genes involved in DNA reparation and efflux pump