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Inflammatory cytokines suppress NAD(P)H:quinone oxidoreductase-1 and induce oxidative stress in cholangiocarcinoma cells

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Abstract

Purpose

The aim of this study was to evaluate the effect of inflammation on NAD(P)H: quinone oxidoreductase-1 (NQO1), the xenobiotic metabolizing and antioxidant enzyme protecting cells against electrophiles and reactive oxygen species in biliary cancer (cholangiocarcinoma) cells.

Methods

Human cholangiocarcinoma cell line, KKU-OCA17 and HeLa Chang liver cells were treated with inflammatory cytokine combinations (interferon-γ, interleukin-1β and tumor necrosis factor-α) for 48 h before NQO1 activity was assayed. Oxidant status was examined by assays of formation of nitric oxide (NO) and superoxide, and glutathione (GSH) levels. Expression of NQO1 was assessed by a reverse transcription and polymerase chain reaction. Effects of S-nitroso-glutathione (GSNO) were examined if the effects of inflammatory cytokines could be mimicked by nitric oxide donor.

Results

NQO1 activity in KKU-OCA17 and HeLa Chang liver cells was suppressed by cytokine combination. Cytokines induced formation of NO and suppression of redox ratios of GSH and glutathione disulfide (GSSG). GSNO produced the similar effects as cytokines on KKU-OCA17, in contrast, GSNO induced increase of NQO1 activity in HeLa Chang liver cells. The treatment of cytokines or GSNO suppressed expression of NQO1 in KKU-OCA17 and HeLa Chang liver cells.

Conclusions

Inflammatory cytokines induced oxidative stress and this is associated with suppression of NQO1, whereas may contribute to differential susceptibility of biliary epithelial cells to chemical-induced cytotoxicity and carcinogenesis.

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Acknowledgments

This work was supported by the Thailand Research Fund (TRF), National Science and Technology Development Agency (NSTDA) and Grant-in-aid from Khon Kaen University. Benjaporn Buranrat is supported by a scholarship from the Commission on Higher Education, the Ministry of Education, and the Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, and Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand

    Auemduan Prawan, Benjaporn Buranrat & Veerapol Kukongviriyapan

  2. Department of Physiology, Faculty of Medicine, and Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand

    Upa Kukongviriyapan

  3. Department of Pathology, Faculty of Medicine, and Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand

    Banchob Sripa

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  1. Auemduan Prawan
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  2. Benjaporn Buranrat
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Correspondence to Veerapol Kukongviriyapan.

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Prawan, A., Buranrat, B., Kukongviriyapan, U. et al. Inflammatory cytokines suppress NAD(P)H:quinone oxidoreductase-1 and induce oxidative stress in cholangiocarcinoma cells. J Cancer Res Clin Oncol 135, 515–522 (2009). https://doi.org/10.1007/s00432-008-0483-2

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  • DOI: https://doi.org/10.1007/s00432-008-0483-2

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