The Cytotoxic Effect of the Benzene Metabolite Hydroquinone is Mediated by the Modulation of MDR1 Expression via the NF-κB Signaling Pathway

Abstract

This is an Open Access article licensed under the terms of the Creative Commons AttributionNonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Key Words Hydroquinone • MDR1 • NF-κB Abstract:Background/Aims: Benzene is a toxic chemical whose leukemogenic effects have been studied for decades. The mechanisms of benzene-induced toxicity and leukemogenicity are not fully understood, although the involvement of several pathways has been suggested, including oxidative stress, DNA damage, cell cycle regulation and programmed cell death. In the present study, we investigated the effect of hydroquinone (HQ), a major benzene metabolite, on the viability of bone marrow derived mesenchymal stem cells (BMSCs) and explored the underlying mechanisms. Methods: First, we study the the effect of HQ on BMSCs cell viability, apoptosis and the expressions of MDR1 and NF-κB. Then we investigate the MDR1 on cell viability and cell apoptosis for BMSCs under HQ treatment. Finally, we studied the impact of nuclear factor κB (NF-κB) on the expression of MDR1. Results: Our results showed that HQ decreased cell viability and promoted cell apoptosis of BMSCs, as determined by the MTT assay and flow cytometry. Western blotting and quantitative PCR showed that HQ downregulated the expression of the MDR1 gene by inhibiting the activation and nuclear translocation of the transcription factor NF-κB. Overexpression of MDR1 attenuated the inhibitory effect of HQ on cell viability in BMSC. Conclusion: The results of the present study suggest the involvement of the multidrug resistance membrane transporter MDR1 and the NF-κB pathway in the cytotoxicity of benzene and its metabolites. Further studies are necessary to clarify the role of the pathways involved and the crosstalk between them in mediating the effects of HQ in bone marrow progenitor cells.J. Huang and M. Zhao contributed equally to this work.

Study of Hydroquinone Mediated Cytotoxicity and Hypopigmentation Effects from UVB-Irradiated Arbutin and DeoxyArbutin

“…HQ may cause oxidative stress, DNA damage, cell cycle regulation, apoptosis, and also increased carcinogenic risk [16,17]. Thus, we analyzed whether UVB-irradiated dA may activate the caspase-3 in Detroit 551 cells.…”

8-Hydroxydeoxyguanosine as a biomarker of oxidative DNA damage in workers exposed to low-dose benzene

“…Based on epidemiological studies, human exposed to high levels of benzene show an increased risk to develop several acute and chronic diseases, such as acute myeloid leukemia, acute and chronic lymphocytic leukemia, non-Hodgkin lymphoma, multiple myeloma and aplastic anaemia [2] . Moreover, exposure to low doses of benzene has been linked to increased incidence of myelodisplastic syndrome and decreased resistance to infection [3] , which may be explained by its immunotoxic activity targeting mainly T-cells [4] .…”

PARP-1 may be involved in hydroquinone-induced apoptosis by poly ADP-ribosylation of ZO-2

“…Previous studies have revealed that different doses of HQ may induce apoptosis ( 24 , 25 ). Treatment with a low dose of HQ for 24 h induced HQ-mediated apoptosis in murine fetal livers and bone marrow hematopoietic cells ( 24 ).…”

“…Treatment with a low dose of HQ for 24 h induced HQ-mediated apoptosis in murine fetal livers and bone marrow hematopoietic cells ( 24 ). Treatment with a high dose of HQ for 24 h promoted apoptosis in bone marrow-derived mesenchymal stem cells ( 25 ). Treatment with 50 or 100 µM HQ for 14 h promoted apoptosis in W7.2 rfau cells ( 26 ).…”