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2005 | 52 | 4 | 953-957
Article title

The effect of new non-cross resistant antitumour agents on the energy state of human erythrocytes

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Multidrug resistance (MDR) of tumour cells is related to the overexpression of ATP-dependent pumps responsible for the active efflux of antitumour agents out of resistant cells. Benzoperimidine and anthrapyridone compounds exhibit comparable cytotoxic activity against sensitive and MDR tumour cells. They diffuse extremely rapidly across the plasma membrane and render the ATP-dependent efflux inefficient. Such uptake could disturb an energy metabolism of normal cells possessing an elevated level of ATP-dependent proteins, especially erythrocytes having a high level of the MRP1, MRP4 and MRP5 proteins. In this study the effect of five antitumour agents: benzoperimidine (BP1), anthrapyridones (CO1, CO7) and reference drugs used in the clinic: doxorubicin (DOX) and pirarubicin (PIRA), on the energetic state in human erythrocytes has been examined. These compounds have various types of structure and kinetics of cellular uptake (slow - DOX, CO7, moderate - PIRA, fast - BP1, CO1) resulting in their different ability to saturate ATP-dependent transporters. The energetic state of erythrocytes was examined by determination of purine nucleotide contents (ATP, ADP, AMP), NAD+ and values of adenylate energy charge (AEC) using an HPLC method. It was found that the level of nucleotides as well as the AEC value of erythrocytes were not changed during 24 h of incubation with these agents independently of their structure and ability to saturate ATP-dependent pumps. This is a very promising result in view of their potential use in the clinic as antitumour drugs against multidrug resistant cancers.
Physical description
  • Department of Biochemistry, University of Szczecin, Szczecin, Poland
  • Department of Biochemistry, University of Szczecin, Szczecin, Poland
  • Department of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, Gdańsk, Poland
  • Department of General Pathology, Pomeranian Medical University, Szczecin, Poland
  • Department of Biochemistry, University of Szczecin, Szczecin, Poland
  • Department of Biochemistry, University of Szczecin, Szczecin, Poland
  • Abraham EH, Sterling KM, Kim RJ, Salikhova AY, Huffman HB, Crockett MA, Johnston N, Parker HW, Boyle WE Jr, Hartov A, Demidenko E, Efird J, Kahn J, Grubman SA, Jefferson DM, Robson SC, Thakar JH, Lorico A, Rappa G, Sartorelli AC, Okunieff P (2001) Blood Cells Mol Dis 27: 165-180.
  • Angle CR, Swanson MS, Stohs SJ, Markin RS (1985) Nephron 39: 169-174.
  • Ataullakhanov FI, Vitvitskii VM, Komarova SV, Mosharov EV (1996) Biokhimiia 61: 266-274.
  • Atkinson DE (1968) Biochemistry 7: 4030-4034.
  • Birchmeier W, Singer SJ (1977) J Cell Biol 73: 647-659.
  • Bobrowska-Hagerstrand M, Wrobel A, Rychlik B, Bartosz G, Soderstrom T, Shirataki Y, Motohashi N, Molnar J, Michalak K, Hagerstrand H (2001) Blood Cells Mol Dis 27: 894-900.
  • Borst P, Evers R, Kool M, Wijnholds J (2000) J Nat Cancer Inst 92: 1295-1302.
  • Bozzi A, Martini F, Leonardi F, Strom R (1994) Biochem Mol Biol Int 32: 95-103.
  • Chaudhary PM, Roninson LB (1993) J Natl Cancer Inst 85: 632-639.
  • Ejendal KF, Hrycyna CA (2002) Curr Protein Pept Sci 3: 503-511.
  • Frezard F, Garnier-Suillerot A (1991) Eur J Biochem 196: 483-491.
  • Gabizon A, Shmeeda H, Barenholz Y (2003) Clin Pharmacokinet 42: 419-436.
  • Garnier-Suillerot A (1995) Curr Pharm Des 1: 69-82.
  • Gewirtz DA (1999) Biochem Pharmacol 57: 727-741.
  • Klokouzas A, Wu CP, van Veen HW, Barrand MA, Hladky SB (2003) Eur J Biochem 270: 3696-3708.
  • Litman T, Druley TE, Stein WD, Bates SE (2001) Cell Mol Life Sci 58: 931-959.
  • Mader RM, Zilg H, Schlappack O, Steger GG, Baur M, Greifenberg B, Heberle U, Dittrich C (1995) Cancer Chemother Pharmacol 37: 91-96.
  • Mankhetkorn S, Dubru F, Hesschenbrouck J, Fiallo M, Garnier-Suillerot A (1996) Mol Pharmacol 49: 532-539.
  • Marbeuf-Gueye C, Broxterman HJ, Dubru F, Priebe W, Garnier-Suillerot A (1998) Mol Pharmacol 53: 141-147.
  • Marbeuf-Gueye C, Ettori D, Priebe W, Kozlowski H, Garnier-Suillerot A (1999) Biochim Biophys Acta 1450: 1-11.
  • Paul S, Breuninger LM, Tew KD, Shen H, Cruh GD (1996) Proc Natl Acad Sci USA 93: 6929-6934.
  • Plasschaert SL, van der Kolk DM, de Bont ESJM, Kamps WA, Morisaki K, Bates SE, Scheffer GL, Scheper RJ, Vellenga E, de Vries EGE (2003) Clin Cancer Res 9: 5171-5177.
  • Robert J (1988) Bull Cancer 75: 167-74.
  • Rychlik B, Pulaski L, Sokal A, Soszynski M, Bartosz G (2000) Acta Biochim Polon 47: 763-772.
  • Rychlik B, Balcerczyk A, Klimczak A, Bartosz G (2003) J Membr Biol 193: 79-90.
  • Simmonds HA, Fairbanks LD, Morris GS, Webster DR, Harley EH (1998) Clin Chim Acta 171: 197-210.
  • Smolenski RT, Lachno DR, Ledingham SJM, Yacoub MH (1990) J Chromatogr 527: 414-420.
  • Stefanska B, Dzieduszycka M, Bontemps-Gracz M, Borowski E, Martelli S, Supino R, Pratesi G, Di Cesare A, Zunino F, Kusnierczyk H, Radzikowski Cz (1999) J Med Chem 42: 3494-3501.
  • Tarasiuk J, Stefanska B, Plodzich I, Tkaczyk-Gobis K, Seksek O, Martelli S, Garnier-Suillerot A, Borowski E (2002) Br J Pharmacol 135: 1513-1523.
  • Tkaczyk-Gobis K, Tarasiuk J, Seksek O, Stefanska B, Borowski E, Garnier-Suilerot A (2001) Eur J Pharmacol 413: 131-141.
  • Traut TW (1994) Mol Cell Biochem 140: 1-22.
  • Wu CP, Klokouzas A, Hladky SB, Ambudkar SV, Barrand MA (2005) Biochem Pharmacol 70: 500-510.
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