Bioreductive activation of mitoxantrone by NADPH cytochrome P450 reductase. Implications for increasing its ability to inhibit the growth of sensitive and multidrug resistant leukaemia HL60 cells

Dorota Kostrzewa-Nowak; Mark Paine; Anna Korytowska; Katarzyna Serwatka; Sylwia Piotrowska; C. Roland Wolf; Jolanta Tarasiuk

doi:10.1016/j.canlet.2006.01.012

Bioreductive activation of mitoxantrone by NADPH cytochrome P450 reductase. Implications for increasing its ability to inhibit the growth of sensitive and multidrug resistant leukaemia HL60 cells

Dorota Kostrzewa-Nowak, Mark Paine, Anna Korytowska, Katarzyna Serwatka, Sylwia Piotrowska, C. Roland Wolf, Jolanta Tarasiuk

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

The aim of this study was to examine the role of reductive activation of mitoxantrone (MX) by human liver NADPH cytochrome P450 reductase (CPR) in increasing its ability to inhibit the growth of human promyelocytic sensitive leukaemia HL60 cell line as well as its MDR sublines exhibiting two different phenotypes of MDR related to the overexpression of P-glycoprotein (HL60/VINC) or MRP1 (HL60/DOX). Our assays showed that the reduction of MX by exogenously added CPR in the presence of low NADPH concentration had no effect in increasing its ability to inhibit the growth of sensitive and MDR tumour cells. In contrast, an important increase in antiproliferative activity of MX after its reductive activation by CPR at high NADPH concentration was observed against HL60/VINC as well as HL60/DOX cells.

Original language	English
Pages (from-to)	252-262
Number of pages	11
Journal	Cancer Letters
Volume	245
Issue number	1-2
DOIs	https://doi.org/10.1016/j.canlet.2006.01.012
Publication status	Published - 8 Jan 2007
Externally published	Yes

Keywords

HL60 human promyelocytic leukaemia
Mitoxantrone
Multidrug resistance
NADPH cytochrome P450 reductase
Reactive metabolites

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10.1016/j.canlet.2006.01.012

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Kostrzewa-Nowak, D., Paine, M., Korytowska, A., Serwatka, K., Piotrowska, S., Wolf, C. R., & Tarasiuk, J. (2007). Bioreductive activation of mitoxantrone by NADPH cytochrome P450 reductase. Implications for increasing its ability to inhibit the growth of sensitive and multidrug resistant leukaemia HL60 cells. Cancer Letters, 245(1-2), 252-262. https://doi.org/10.1016/j.canlet.2006.01.012

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title = "Bioreductive activation of mitoxantrone by NADPH cytochrome P450 reductase. Implications for increasing its ability to inhibit the growth of sensitive and multidrug resistant leukaemia HL60 cells",

abstract = "The aim of this study was to examine the role of reductive activation of mitoxantrone (MX) by human liver NADPH cytochrome P450 reductase (CPR) in increasing its ability to inhibit the growth of human promyelocytic sensitive leukaemia HL60 cell line as well as its MDR sublines exhibiting two different phenotypes of MDR related to the overexpression of P-glycoprotein (HL60/VINC) or MRP1 (HL60/DOX). Our assays showed that the reduction of MX by exogenously added CPR in the presence of low NADPH concentration had no effect in increasing its ability to inhibit the growth of sensitive and MDR tumour cells. In contrast, an important increase in antiproliferative activity of MX after its reductive activation by CPR at high NADPH concentration was observed against HL60/VINC as well as HL60/DOX cells.",

keywords = "HL60 human promyelocytic leukaemia, Mitoxantrone, Multidrug resistance, NADPH cytochrome P450 reductase, Reactive metabolites",

author = "Dorota Kostrzewa-Nowak and Mark Paine and Anna Korytowska and Katarzyna Serwatka and Sylwia Piotrowska and Wolf, \{C. Roland\} and Jolanta Tarasiuk",

year = "2007",

month = jan,

day = "8",

doi = "10.1016/j.canlet.2006.01.012",

language = "English",

volume = "245",

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journal = "Cancer Letters",

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Kostrzewa-Nowak, D, Paine, M, Korytowska, A, Serwatka, K, Piotrowska, S, Wolf, CR & Tarasiuk, J 2007, 'Bioreductive activation of mitoxantrone by NADPH cytochrome P450 reductase. Implications for increasing its ability to inhibit the growth of sensitive and multidrug resistant leukaemia HL60 cells', Cancer Letters, vol. 245, no. 1-2, pp. 252-262. https://doi.org/10.1016/j.canlet.2006.01.012

Bioreductive activation of mitoxantrone by NADPH cytochrome P450 reductase. Implications for increasing its ability to inhibit the growth of sensitive and multidrug resistant leukaemia HL60 cells. / Kostrzewa-Nowak, Dorota; Paine, Mark; Korytowska, Anna et al.
In: Cancer Letters, Vol. 245, No. 1-2, 08.01.2007, p. 252-262.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Bioreductive activation of mitoxantrone by NADPH cytochrome P450 reductase. Implications for increasing its ability to inhibit the growth of sensitive and multidrug resistant leukaemia HL60 cells

AU - Kostrzewa-Nowak, Dorota

AU - Paine, Mark

AU - Korytowska, Anna

AU - Serwatka, Katarzyna

AU - Piotrowska, Sylwia

AU - Wolf, C. Roland

AU - Tarasiuk, Jolanta

PY - 2007/1/8

Y1 - 2007/1/8

N2 - The aim of this study was to examine the role of reductive activation of mitoxantrone (MX) by human liver NADPH cytochrome P450 reductase (CPR) in increasing its ability to inhibit the growth of human promyelocytic sensitive leukaemia HL60 cell line as well as its MDR sublines exhibiting two different phenotypes of MDR related to the overexpression of P-glycoprotein (HL60/VINC) or MRP1 (HL60/DOX). Our assays showed that the reduction of MX by exogenously added CPR in the presence of low NADPH concentration had no effect in increasing its ability to inhibit the growth of sensitive and MDR tumour cells. In contrast, an important increase in antiproliferative activity of MX after its reductive activation by CPR at high NADPH concentration was observed against HL60/VINC as well as HL60/DOX cells.

AB - The aim of this study was to examine the role of reductive activation of mitoxantrone (MX) by human liver NADPH cytochrome P450 reductase (CPR) in increasing its ability to inhibit the growth of human promyelocytic sensitive leukaemia HL60 cell line as well as its MDR sublines exhibiting two different phenotypes of MDR related to the overexpression of P-glycoprotein (HL60/VINC) or MRP1 (HL60/DOX). Our assays showed that the reduction of MX by exogenously added CPR in the presence of low NADPH concentration had no effect in increasing its ability to inhibit the growth of sensitive and MDR tumour cells. In contrast, an important increase in antiproliferative activity of MX after its reductive activation by CPR at high NADPH concentration was observed against HL60/VINC as well as HL60/DOX cells.

KW - HL60 human promyelocytic leukaemia

KW - Mitoxantrone

KW - Multidrug resistance

KW - NADPH cytochrome P450 reductase

KW - Reactive metabolites

U2 - 10.1016/j.canlet.2006.01.012

DO - 10.1016/j.canlet.2006.01.012

M3 - Article

SN - 0304-3835

VL - 245

SP - 252

EP - 262

JO - Cancer Letters

JF - Cancer Letters

IS - 1-2

ER -

Bioreductive activation of mitoxantrone by NADPH cytochrome P450 reductase. Implications for increasing its ability to inhibit the growth of sensitive and multidrug resistant leukaemia HL60 cells

Abstract

Keywords

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