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t-AUCB, an improved sEH inhibitor, suppresses human glioblastoma cell growth by activating NF-κB-p65

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Abstract

Although sEH inhibitors are well studied in inflammatory and cardiovascular diseases, their effects on gliomas are unclear. In this study, we investigated the effects of t-AUCB, a more potent and selective sEH inhibitor, on U251 and U87 human glioblastoma cell lines and the HepG2 human hepatocellular carcinoma cell line. Our results showed that t-AUCB efficiently inhibited sEH activities in all three cell lines (the inhibition rate was more than 80% in each) and suppressed U251 and U87 cell growth in a dose-dependent manner, but exhibited no cell growth inhibition on HepG2. We detected high levels of phosphorylated NF-κB-p65 (Ser536) in t-AUCB-treated U251 and U87 cells, and then found that the NF-κB inhibitor PDTC can completely abolish t-AUCB-induced growth inhibition. This indicated that t-AUCB suppresses U251 and U87 cell growth by activating NF-κB-p65. Moreover, we found that t-AUCB induces cell-cycle G0/G1 phase arrest by regulating Cyclin D1 mRNA and protein levels and CDC2 (Thr161) phosphorylation level. We propose to further test this promising reagent for its anti-glioma activity in clinical relevant orthotopic brain glioma models.

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Acknowledgements

We thank Professor Bruce D. Hammock for providing the sEH inhibitor t-AUCB, Professor Kun Yao for providing U251 and U87 human glioblastoma cell lines and Doctor Wenjie Zhang for providing HepG2 human hepatocellular carcinoma cell line for these experiments. This study was supported by Jiangsu Province Science Fund (Number BK2007257).

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Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China

    Junyang Li, Biao Xing, Gong Chen, Bing Gu, Guofeng Zhang, Dong Wei, Peiyuan Gu, Meng Li & Weixing Hu

  2. Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, 264 Guangzhou Road, Nanjing, 210029, China

    Hongyi Liu

  3. Department of Pneumology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

    Yanzhe Yu & Hui Wang

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  1. Junyang Li
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Correspondence to Weixing Hu.

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Li, J., Liu, H., Xing, B. et al. t-AUCB, an improved sEH inhibitor, suppresses human glioblastoma cell growth by activating NF-κB-p65. J Neurooncol 108, 385–393 (2012). https://doi.org/10.1007/s11060-012-0841-4

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  • DOI: https://doi.org/10.1007/s11060-012-0841-4

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