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Experimental Hematology & Oncology
Published in: Experimental Hematology & Oncology 1/2015

Open Access 01-12-2015 | Research

Activation of NQO1 in NQO1*2 polymorphic human leukemic HL-60 cells by diet-derived sulforaphane

Authors: Joseph M. Wu, Ardalan Oraee, Barbara B. Doonan, John T. Pinto, Tze-chen Hsieh

Published in: Experimental Hematology & Oncology | Issue 1/2015

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Abstract

Background

The NAD(P)H: quinone oxidoreductase (NQO1) confers protection against semiquinones and also elicits oxidative stress. The C609T polymorphism of the NQO1 gene, designated NQO1*2, significantly reduces its enzymatic activity due to rapid degradation of protein. Since down regulation of NQO1 mRNA expression correlates with increased susceptibility for developing different types of cancers, we investigated the link between leukemia and the NQO1*2 genotype by mining a web-based microarray dataset, ONCOMINE. Phytochemicals prevent DNA damage through activation of phase II detoxification enzymes including NQO1. Whether NQO1 expression/activity in leukemia cells that carry the labile NQO1*2 genotype can be induced by broccoli-derived phytochemical sulforaphane (SFN) is currently unknown.

Methods and Results

The ONCOMINE query showed that: (1) acute lymphoblastic leukemia and chronic myelogenous leukemia are associated with reduced NQO1 levels, and (2) under-expressed NQO1 was found in human HL-60 leukemia cell line containing the heterozygous NQO1*2 polymorphism. We examined induction of NQO1 activity/expression by SFN in HL-60 cells. A dose-dependent increase in NQO1 level/activity is accompanied by upregulation of the transcription factor, Nrf2, following 1–10 μM SFN treatment. Treatment with 25 µM SFN drastically reduced NQO1 levels, inhibited cell proliferation, caused sub-G1 cell arrest, and induced apoptosis, and a decrease in the levels of the transcription factor, nuclear factor-κB (NFκB).

Conclusions

Up to 10 μM of SFN increases NQO1 expression and suppresses HL-60 cell proliferation whereas ≥ 25 μM of SFN induces apoptosis in HL-60 cells. Further, SFN treatment restores NQO1 activity/levels in HL-60 cells expressing the NQO1*2 genotype.
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Metadata
Title
Activation of NQO1 in NQO1*2 polymorphic human leukemic HL-60 cells by diet-derived sulforaphane
Authors
Joseph M. Wu
Ardalan Oraee
Barbara B. Doonan
John T. Pinto
Tze-chen Hsieh
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Experimental Hematology & Oncology / Issue 1/2015
Electronic ISSN: 2162-3619
DOI
https://doi.org/10.1186/s40164-016-0056-z

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