Role of three main ABC transporters in multidrugresistance

Multidrug resistance is one of the major barriers to successful cancerchemotherapy, That occurs when cancer cells spontaneously becomeinsensitive to drugs that are structurally unrelated. One of the mechanismsinvolved in drug resistance is the overexpression of ATP-Binding Cassette(ABC) transporters. Drug excretion by ABC transporters reduces theintracellular concentration of drugs and causes chemotherapy to fail. Thesemembrane transporters are proteins that belong to a gene family called ABCtransporters.The ABC superfamily is the largest protein transporter superfamily found inall living organisms. In humans, there are ۴۹ known ABC genes classifiedinto seven different families (A–G) depending on their amino acid sequenceand eventually their protein domains. There are ۱۲ transporters reported to beresponsible for drug efflux, however, three main MDR transporters P-gp (Pglycoprotein),MRP۱ (Multidrug resistance-associated protein ۱), and BCRP(Breast cancer resistance protein) have a great significance in the efflux of avariety of drugs and the genes encoding these transportersare ABCB۱, ABCC۱and ABCG۱ in order. P-gp is the first efflux transporterdiscovered and BCRP is the most recently ABC protein identified to beinvolved in multidrug resistance. this review describes the drug resistance andsome of the characteristics of the three main transporters

Keywords:

Multidrug resistance , ABC transporters , P-glycoprotein (P-gp) , Multidrug resistance-associated protein ۱ (MRP۱) , Breast cancer resistanceprotein (BCRP)