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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

Content
Title variants
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EN
Abstracts
EN
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.
Publisher

Year
Volume
52
Issue
4
Pages
953-957
Physical description
Dates
published
2005
received
2005-06-24
revised
2005-09-27
accepted
2005-10-14
(unknown)
2005-10-25
Contributors
author
  • 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
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Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv52p953kz
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