eptides selected from artificial peptide libraries have special interest in cell targeting, drug discovery, molecular diagnosis and multidrug reversal. Peptides selected from artificial peptide libraries against doxorubicin resistant K562 cells have the capacity in the reversal of the doxorubicin resistance. Our aim is to determine the characteristics of these peptides on recombinant human P-glycoprotein membrane fractions to be able to understand their interactions. Peptides were selected against doxorubicin resistant K562 cells. The effects of synthesized peptides on these cells viability was done by XTT viability assay. The interactions of peptides with P-glycoprotein were done by Pgp-GloTM Assay System by measuring the ATPase activity of P-glycoprotein. According to our results; four selected peptides effected on doxorubicin resistant K562 cells viability and stimulated the P-glycoprotein activity in the presence of doxorubicin at different levels. If the P-glycoprotein stimulation occurs on living doxorubicin resistant K562 cells, cell viability will not be affected due to multidrug resistance effect of P-glycoprotein. Peptides selected from artificial peptide libraries are useful tools in the reversal of multidrug resistance and for understanding the membrane structure-function relationships.
___
Iqbal MP. Mechanisms of Drug Resistance in Cancer Cells. Pak J Med Sci. 2003;19:118-27.
Hamada H, Tsuruo T. Purification of the 170- to 180-kilodalton membrane glycoprotein associated with multidrug resistance. 170- to 180-kilodalton membrane glycoprotein is an ATPase. J Biol Chem. 1988;263(3):1454-8.
Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I, Gottesman MM. Biochemical, Cellular and Pharmacological Aspects of the Multidrug Transporter. Annu Rev Pharmacol Toxicol. 1999;39:361-98.
Litman T, Skovsgaard T, Stein WD. Pumping of Drugs by P-Glycoprotein: A Two-Step Process? J Pharmacol Exp Ther. 2003;307(3):846-53.
Glavinas H, Krajcsi P, Cserepes J, Sarkadi B.The role of ABC transporters in drug resistance, metabolism and toxicity. Curr Drug Del. 2004;1(1):27-42.
Matsunaga T, Kose E, Yasuda S, Ise H, Ikeda U, Ohmori S. Determination of p-glycoprotein ATPase activity using luciferase. Biol Pharm Bull. 2006;29(3):560-4.
Mercer SL, Hassan H, Cunningham CW, Eddington ND, Coop A. Opioids and efflux transporters. Part 1: P-glycoprotein substrate activity of N-substituted analogs of meperidine. Bioorg Med Chem Lett. 2007;17(5):1160-2.
Duan Z, Choy E, Hornicek FJ. NSC23925, identified in a high-throughput cellbased screen, reverses multidrug resistance. PLoS ONE 2009;4(10):e7415.
Susa M, Choy E, Yang C, Schwab J, Mankin H, Hornicek F, Duan Z. Multidrug resistance reversal agent, NSC77037, identified with a cell-based screening assay. J Biomol Screening. 2010;15(3):287-96.
Smith GP, Petrenko VA. Phage Display. Chem Rev. 1997;97(2):391-410.
Rumjanek VM, Trindade GS, Wagner-Souza K, de-Oliveira MC, MarquesSantos LF, Maia RC, Capella MA. Multidrug resistance in tumor cells: characterization of the multidrug resistant cell line K562-Lucena 1. Annu Acad Bras Ci. 2001;73(1):57-69.
Arora A, Seth K, Shukla Y. Reversal of P-glycoprotein-mediated multidrug resistance by diallyl sulfide in K562 leukemic cells and in Mouse liver. Carcinogenesis. 2004;25(6):941-9.
Maxwell DJ, Hicks BC, Parsons S, Sakiyama-Elbert SE. Development of rationally designed affinity-based drug delivery systems. Acta Biomaterial. 2005;1(1):101-13.
Arikan SY, Atalay A, Atalay EO. Interaction of Peptides Selected from Artificial Peptide Library With Doxorubicin Resistant K562 Cells. Int J Cancer Res. 2010;6:251-6.
Vivès E, Schmidt J, Pèlegrin A. Cell-penetrating and cell-targeting peptides in drug delivery. Biochim Biophys Acta. 2008;1786(2):126-38.
Lo A, Lin CT, Wu HC. Hepatocellular carcinoma cell-specific peptide ligand for targeted drug delivery. Mol Cancer Ther. 2008;7(3):579–89.
Zhang B, Zhang Y, Wang J, Zhang Y, Chen J, Pan Y, Ren L, Hu Z, Zhao J, Liao M, Wang S. Screening and Identification of a Targeting Peptide to Hepatocarcinoma from a Phage Display Peptide Library. Mol Med. 2007;13(5-6):246-54.
Benhar I. Biotechnological applications of phage and cell display. Biotechnol Adv. 2001;19(1):1-33.
Bar H, Yacoby I, Benhar I. Killing cancer cells by targeted drug-carrying phage nanomedicines. BMC Biotechnol. 2008;8:37.
Lozzio CB, Lozzio BB. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood. 1975;45(3):321-34.
Hait WN, Choudhury S, Srimatkandada S, Murren JR. Sensitivity of K562 human chronic myelogenous leukemia blast cells transfected with a human multidrug resistance cDNA to cytotoxic drugs and differentiating agents. J Clin Invest. 1993;91(5):2207-15.
Koeffler HP, Golde DW. Human myeloid leukemia cell line: a review. Blood. 1980;56(3):344-50.
Dos Santos GG, Reinders J, Ouwehand K, Rustemeyer T, Scheper RJ, Gibbs S. Progress on the development of human in vitro dendritic cell based assays for assessment of the sensitizing potential of a compound. Toxicol Appl Pharmacol. 2009;236(3):372-82.
Lee SJ, Kim KH, Park JS, Jung JW, Kim YH, Kim SK, Kim WS, Goh H, Kim S, Yoo J, Kim DW, Kim KP. Comparative analysis of cell surface proteins in chronic and acute leukemia cell lines. Biochem Biophysic Res Comm. 2007;357(3):620-6.
Kim RB. Drugs as P-glycoprotein substrates, inhibitors and inducers. Drug Met Rev. 2002;34(1-2):47-54.
Tsuruo T. (1988) Mechanisms of Multi Drug Resistance and Implications for Therapy. Jpn J Cancer Res. 1988;79(3):285-96.
Tao L, Li J, Zhang J. Brazilein overcame ABCB1-mediated multidrug resistance in human leukaemia K562/AO2 cells. Afr J Pharm Pharmaco. 2011;5:1937-44.