leukotriene-c4 and Neoplasms

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.

Topics: Antineoplastic Agents; Biological Transport; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Glutathione; Humans; Leukotriene C4; Multidrug Resistance-Associated Proteins; Neoplasms; Tissue Distribution

Aberrant arachidonic acid metabolism has recently received intensive attention in the field of cancer research. Recent discoveries regarding the long-term cardiovascular side effects of cyclooxygenase 2 inhibitors have cast doubts on their use for cancer chemoprevention. Although such a problem does not undermine the importance of cyclooxygenase 2 as a cancer chemopreventive target, investigation into other AA-metabolizing pathways that are also important in inflammation and inflammation-associated carcinogenesis is necessary. Here, the important role of the 5-lipoxygenase pathway in carcinogenesis is reviewed. Inhibition of the 5-lipoxygenase pathways clearly has chemopreventive effects on various cancers, and hence further studies on its enzymes, metabolites and receptors for cancer chemoprevention and therapy are warranted.

Topics: 5-Lipoxygenase-Activating Proteins; Animals; Anticarcinogenic Agents; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Carrier Proteins; Enzyme Inhibitors; Humans; Leukotriene B4; Leukotriene C4; Lipoxygenase Inhibitors; Membrane Proteins; Neoplasms; Receptors, Leukotriene; Receptors, Leukotriene B4