VEGA 2/0155/09

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Changes of leukemia cells associated with P-glycoprotein mediated multidrug resistance development       

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Principal investigator: Albert Breier

Duration: January 2009 – December 2011
Coordinating institution: Institute of Molecular Physiology and Genetics, SAS, Bratislava

Annotation:

We plan to find processes associated with P-glycoprotein (Pgp) mediated multidrug resistance (MDR) development in neoplastic cells. Overexpression of Pgp in neoplastic cells is often induced by adaptation of cells to cytotoxic effects of several substances in their sublethal concentrations. Several changes of cell regulation and metabolic pathways are involved in the development of this type of MDR together with massive overexpression of Pgp and these changes are responsible for alteration in several cell processes like energy production, protein phosphorylation or entering to apoptosis etc. These alterations may be induced directly by overexpression of Pgp or by chemical stress during cell adaptation. The aim of this project is to recognize which one from the latter two possibilities is valid in the respective changes associated with this type of MDR. We will use mice leukemia L1210 cells that overexpress Pgp due to adaptation to vincristine or due to stable transfection with human mdr1 gene encoding Pgp.

Publications:
pdf Sulova Z, Brtko J, Macejová D, Breier A: Are Nuclear Receptors for Retinoids Involved in the Control of the Expression and Activity of P-Glycoprotein? In Retinoic Acid: Structure, Mechanisms and Roles in Disease (Cheng, L.H., It, Y. eds.) NOVA Publisher, 2012 pp. 29-52.
Breier A, Gibalova L, Seres M, Barancik M, Sulova Z: P-glycoprotein mediated multidrug resistance of cancer tissue: Implication for cancer chemotherapy. ISBN 978-80-89233-55-7, PETRUS Publisher, 2012
PubMed Breier A, Gibalova L, Seres M, Barancik M, Sulova Z. New insight into p-glycoprotein as a drug target. Anti-cancer Agents Med Chem. 13 (2013) 159-70. (IF2012=2.610)
PubMed Barancik M, Bohacova V, Gibalova L, Sedlak J, Sulova Z, Breier A. Potentiation of Anticancer Drugs: Effects of Pentoxifylline on Neoplastic Cells. Int. J. Mol. Sci. 13 (2012) 369-382
 
PubMed Bubencíkova T, Cholujová D, Messingerová L, Mislovicova D, Seres M, Breier A, Sulova Z. Detection of glycomic alterations induced by overexpression of p-glycoprotein on the surfaces of l1210 cells using sialic Acid binding lectins. Int J Mol Sci. 13, (2012) 15177-15192
 
PubMed Gibalová L, Sereš M, Rusnák A, Ditte P, Labudová M, Uhrík B, Pastorek J, Sedlák J, Breier A, Sulová Z. P-glycoprotein depresses cisplatin sensitivity in L1210 cells by inhibiting cisplatin-induced caspase-3 activation. Toxicol In Vitro. 26 (2012) 435-444. (IF2012=2.650)
PubMed Šereš M, Cholujová D, Bubenčíkova T, Breier A, Sulová Z. Tunicamycin depresses p-glycoprotein glycosylation without an effect on its membrane localization and drug efflux activity in l1210 cells. Int J Mol Sci. 12 (2011) 7772-7784. (IF2012=2.464)