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

100%

Nowak R., Baranowska-Bosiacka I., Stefańska B., Machaliński B., Hłyńczak A. J., Tarasiuk J.

2005

vol. 52

issue 4

953-957

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.

Conjugated linoleic acids regulate triacylglycerol and cholesterol concentrations in macrophages/foam cells by the modulation of CD36 expression

84%

Stachowska E., Baskiewicz M., Marchlewicz M., Czupryńska K., Kaczmarczyk M., Wiszniewska B., Machaliński B., Chlubek D.

2010

vol. 57

issue 3

379-384

Atherosclerosis is an inflammatory disease characterised by the accumulation of lipids and their metabolites in the artery wall. During inflammation circulating LDL are taken up by macrophages through two major scavenger receptors: CD36 and scavenger receptor A (SRA). Fatty acids that are common in food, e.g. linoleic acid and n-3 unsaturated fatty acids can modulate expression of CD36 on the macrophage surface. Conjugated linoleic acid isomers (CLA) that originate from the human diet, have demonstrated antiatherogenic properties in several experiments. Animal study evidenced that CLA could induce resolution of plaque by activation of peroxisome proliferator activated receptors and down-regulation of pro-inflammatory genes. Less unequivocal results were obtained in human studies (on the CLA effects on the inflammatory process). Therefore in this study we investigated the influence of CLA on CD36 expression and lipid accumulation in human macrophages. Macrophages were incubated with 30 µM cis-9,trans-11 CLA, trans-10,cis-12 CLA or linoleic acid for 48 h. After that, expression of CD36 as well as accumulation of lipids were measured by flow cytometry, microscopy and a spectroscopic method. We demonstrate that both cis-9,trans-11 C 18:2 CLA and linoleic acid slightly elevated expression of CD36, whereas second isomer - trans-10,cis-12 CLA - did not. Nevertheless, only trans-10,cis-12 CLA triggered delipidation of macrophages, that is decreased triacylglycerols concentration. Also in human adipocytes, trans-10,cis-12 CLA causes cell delipidation by reduction of PPAR receptor expression. We propose a similar mechanism for human macrophages/foam cells.

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2 Acta Biochimica Polonica

1 2010

1 2005

2 Machaliński B.

1 Baranowska-Bosiacka I.

1 Baskiewicz M.

1 Chlubek D.

1 Czupryńska K.

1 Hłyńczak A. J.

1 Kaczmarczyk M.

1 Marchlewicz M.

1 Nowak R.

1 Stachowska E.

1 Stefańska B.

1 Tarasiuk J.

1 Wiszniewska B.

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

Conjugated linoleic acids regulate triacylglycerol and cholesterol concentrations in macrophages/foam cells by the modulation of CD36 expression