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


CONCLUSIONS
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.
Jianshu
J
Huang
Mingdong
M
Zhao
Xiuju
X
Li
Li
L
Ma
Jihong
J
Zhang
Jimin
J
Shi
Bing
B
Li
Wei
W
Fan
Yuanling
Y
Zhou
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation; D006873:Hydroquinones / Q000633:toxicity*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction
D018435:ATP Binding Cassette Transporter, Subfamily B; D006873:Hydroquinones; D016328:NF-kappa B