Multidrug resistance associated proteins in multidrug resistance

Abstract

Multidrug resistance proteins (MRPs) are members of the C family of a group of proteins named ATP-binding cassette (ABC) transporters. These ABC transporters together form the largest branch of proteins within the human body. The MRP family comprises of 13 members, of which MRP1 to MRP9 are the major transporters indicated to cause multidrug resistance in tumor cells by extruding anticancer drugs out of the cell. They are mainly lipophilic anionic transporters and are reported to transport free or conjugates of glutathione (GSH), glucuronate, or sulphate. In addition, MRP1 to MRP3 can transport neutral organic drugs in free form in the presence of free GSH. Collectively, MRPs can transport drugs that differ structurally and mechanistically, including natural anticancer drugs, nucleoside analogs, antimetabolites, and tyrosine kinase inhibitors. Many of these MRPs transport physiologically important anions such as leukotriene C4, bilirubin glucuronide, and cyclic nucleotides. This review focuses mainly on the physiological functions, cellular resistance characteristics, and probable in vivo role of MRP1 to MRP9.

Nanoparticle delivery of anticancer drugs overcomes multidrug resistance in breast cancer

“…MRP1 is able to confer resistance to anthracyclines, vinca alkaloids, epipodo-phyllotoxins, camptothecins and methotrexate, but not to taxanes, which are an important component of the P-gp profile. Besides, MRP1 is related to accelerated relapse in breast cancer, and a negative correlation between MRP1 expression and response to treatment has been found (Kruh & Belinsky, 2003;Sodani et al, 2012).…”

“…Similar to P-gp MRP1 has been extensively studied over the past 25 years because of its prominent role in conferring multidrug resistance. MRP1 is a 190 kDa protein, consisting of 17 transmembrane domains with a P-gp-like core, but an additional N-terminal membrane spanning domain (TMD0) is present (Kruh & Belinsky, 2003;Leonessa & Clarke, 2003;Sodani et al, 2012). MRP1 is a basolateral transporter, the activity of which results in the movement of compounds into tissues that lie beneath the basement membrane.…”

Doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer

“…3 The most commonly reported efflux membrane transporter MDR-associated proteins (MRPs) are extensively overexpressed in various tumor cells and actively pump the broad spectrum of chemotherapeutics outward from the cells. 4,5 Several chemotherapeutics can be served as substrates for MRPs. 6,7 The antitumor agent doxorubicin (DOX) is widely used for the treatment of various solid tumors via interacting with DNA through intercalation and inhibiting topoisomerase II, but it is also a substrate for MRPs.…”

How to overcome ATP-binding cassette drug efflux transporter-mediated drug resistance?

“…Depending on expression levels, MRP1 can confer resistance to a variety of antineoplastic drugs, including vinca alkaloids, anthracyclines, epipodophyllotoxins, saquinavir, methotrexate, mitoxantrone, camptothecins, paclitaxel, glucuronide, doxorubicin, epirubicin, and tyrosine kinase inhibitors such as imatinib [57,58] . High MRP1 expression levels have been identified in different cancer types, e.g., lung cancer, breast cancer, prostate cancer, gastrointestinal carcinoma, melanoma, neuroblastoma, ovarian and hematological malignancies [44,59] (AML, ALL and chronic lymphoblastic leukemia).…”