Abstract
The aim of this study was to examine the effect of selected pyridinium salts, 1-methyl-3-nitropyridine chloride (MNP(+)Cl(-)) and 3,3,6,6,10-pentamethyl-3,4,6,7-tetrahydro-[1,8(2H,5H)-dion]acridine chloride (MDION(+)Cl(-)), on the activity of doxorubicin (DOX) and vincristine (VINC) towards human promyelocytic leukaemia HL60 cells as well as its multidrug resistant (MDR) sublines exhibiting two different phenotypes of MDR related to the overexpression of P-glycoprotein (HL60/VINC) or MRP1 (HL60/DOX). MNP and MDION salts were much less cytotoxic themselves (about 100-fold and 2000-fold compared with DOX and VINC, respectively) against HL60 cells but, in contrast to DOX and VINC, they conserved an important cytotoxic activity towards resistant HL60/VINC and HL60/DOX cells (resistance factor, RF = 2-4.5). It was shown that MNP(+)Cl(-) and MDION(+)Cl(-) increased the cytotoxicity of non-bioreductive antitumour agent VINC towards human promyelocytic leukaemia HL60 cells and its resistant sublines HL60/VINC and HL60/DOX. However, in the case of DOX the decrease in its cytotoxic activity towards all studied cell lines was observed in the presence of MNP(+)Cl(-) and MDION(+)Cl(-). Presented data suggest that the bioreductive drug DOX, ...Continue Reading
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