NADPH-Cytochrome P450 Reductase Is Regulated by All-Trans Retinoic Acid and by 1,25-Dihydroxyvitamin D.sub.3 in Human Acute Myeloid Leukemia Cells

Acute myeloid leukemia (AML) cell lines can be driven to differentiate to monocyte-like cells by 1,25- dihydroxyvitamin D.sub.3 (1,25D) and to granulocyte-like cells by all-trans-retinoic acid (ATRA). Both compounds activate their specific intracellular receptors, vitamin D receptor (VDR) and retino...

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Bibliographic Details
Published inPloS one Vol. 9; no. 3; p. e91752
Main Authors Gocek, Elzbieta, Marchwicka, Aleksandra, Bujko, Kamila, Marcinkowska, Ewa
Format Journal Article
LanguageEnglish
Published Public Library of Science 18.03.2014
Subjects
Acute myelocytic leukemia
Cytochrome P-450
Electron transport
Metabolites
Physiological aspects
RNA
Vitamin D
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Summary:Acute myeloid leukemia (AML) cell lines can be driven to differentiate to monocyte-like cells by 1,25- dihydroxyvitamin D.sub.3 (1,25D) and to granulocyte-like cells by all-trans-retinoic acid (ATRA). Both compounds activate their specific intracellular receptors, vitamin D receptor (VDR) and retinoic acid receptors (RARs) respectively. Inside the cells 1,25D is degraded to calcitrioic acid by a mitochondrial enzyme CYP24A1, while ATRA is degraded to several polar metabolites by CYP26. NADPH-cytochrome P450 oxidoreductase (POR) is a membrane-bound enzyme required for electron transfer to cytochrome P450 (CYP), vital in the processes of the metabolism of drugs and steroid production in humans. In this paper we report that POR in AML cells, from both cell lines and patients, is upregulated by ATRA and by 1,25D at the level of mRNA and protein. Partial silencing of POR in HL60 cells resulted in augmented differentiation response to 1,25D.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0091752