Proteins in cancer multidrug resistance
Journal Title: Advances in Hygiene and Experimental Medicine - Year 2014, Vol 68, Issue
Abstract
Multidrug Resistance (MDR) is defined as insensitivity to administered medicines that are structurally unrelated and have different molecular targets. Cancers possess numerous mechanisms of drug resistance, involving various aspects of cell biology. A pivotal role in this phenomenon is played by proteins – enzymatic or structural parts of the cell.Membrane transporters, including the main members of ABC protein family – P-gp, MRP1 and BCRP, as well as LRP, which builds structure of vaults, determine the multidrug-resistant phenotype by decreasing drug concentration within the cell or modifying its distribution to intracellular compartments. The π isoform of protein enzyme – glutathione S-transferase (GSTP-1), is responsible for excessive intensity of detoxification of cytostatics. A common example of altered drug target site that does not respond to chemotherapy is topoisomerase II α (TopoIIa). Alterations of programmed cell death result from expression of metallothionein (MT) – inhibitor of the process, and cytokeratin 18 (CK18), which, if in high concentration, also prevents apoptosis of cells.Several methods of decreasing activity of these proteins have been developed, aiming to overcome MDR in cancer cells. However, for a variety of reasons, their clinical suitability is still very low, leading to continuous increase in death rate among patients. This paper presents current state of knowledge on the most important examples of proteins responsible for MDR of cancer cells and molecular mechanisms of their action.
Authors and Affiliations
Marta Popęda, Elżbieta Płuciennik, Andrzej K. Bednarek
Keywords
Related Articles
- EP ID EP67382
- DOI -
- Views 117
- Downloads 0
Drugs affecting the incretin system and renal glucose transport: do they meet the expectations of modern therapy of type 2 diabetes?
Agents introduced into therapy of type 2 diabetes in the last few years are still the subject of numerous clinical and experimental studies. Although many studies have been completed, we still do not know all aspects of...
Antibacterial Activity of Selected Standard Strains of Lactic Acid Bacteria Producing Bacteriocins – Pilot Study
Introduction: In this paper, an attempt was made to evaluate the antibacterial potential of standard strains of lactic acid bacteria (LAB) producing bacteriocins of various classes, thus demonstrating various mechanisms...
Hemoglobina – źródłem reaktywnych form tlenu
Erytrocyty to komórki wyjątkowo podatne na działanie reaktywnych form tlenu głównie dlatego, iż biorą udział w transporcie tlenu, przez co są bezpośrednio narażone na jego działanie. Ponadto zawarta w erytrocycie hemoglo...
Cyclic guanosine monophosphate in the regulation of the cell function
Intracellular concentration of cGMP depends on the activity of guanylate cyclase, responsible for its synthesis, on the activity of cyclic nucleotide degrading enzymes - phosphodiesterases (PDEs). There are two forms of...
The role of intestinal microbiota in irritable bowel syndrome
In recent years, impressive advances in the knowledge about a vast number of microbes living in the human body and interactions between the microbiota and the human body have been observed. All micro-organisms that live...