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IKKβ downregulation is critical for triggering JNKs-dependent cell apoptotic response in the human hepatoma cells under arsenite exposure

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Abstract

Arsenite has a long history in treating leukemia, which might be also effective in the therapy of other cancers. Our previous published data have demonstrated that arsenite exposure induces apoptosis in the HepG2 human hepatoma cells via activating JNKs/AP-1 pathway, but the upstream signaling events responsible for JNKs (c-Jun N-terminal kinase) cascade activation have not been fully discovered. Since cross-talk between IKK/NF-κB and JNKs pathways under stress conditions is a hot topic, in this article, we investigate the potential roles of IKKα and IKKβ, the catalytic subunits of IKK complexes, in the arsenite-induced JNKs pathway activation in the HepG2 cells. We found that arsenite exposure induced JNKs and AP-1 activation accompanying with a significant reduction of both IKKα and IKKβ expressions. Overexpression of IKKβ, but not of IKKα, inhibited arsenite-induced MKK7/JNKs/AP-1 pathway activation as well as the apoptotic response. Therefore, we conclude that the downregulation of IKKβ expression is the prerequisite signaling event for mediating JNKs pathway activation and the cellular apoptotic response in the HepG2 cells under arsenite exposure. Targeting IKKβ might be helpful to enhance the tumor therapeutic effect of arsenite.

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Acknowledgments

This project is supported by the National Natural Science Foundation of China No. 30871277 and 30970594, Beijing Natural Science Foundation 5092022 and 5102035, and the National Key Research and Development Programs on Fundamental Sciences (973 Project) 2011CB503803 to Dr. Lun Song.

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Authors and Affiliations

  1. Department of Cellular Immunology, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing, 100850, People’s Republic of China

    Yi Li, Yi Hao, Ming Gao, Wen Dong, Meiru Hu & Lun Song

  2. Department of New Drug Screening Center, School of Chinese Pharmaceutical University, No. 24 Tong Jia Xiang St, Nanjing, 210009, People’s Republic of China

    Yi Li & Shengtao Yuan

  3. Department of Pathology, School of Basic Medical Sciences, Lanzhou University, Tianshui South Road, Lanzhou, 730000, People’s Republic of China

    Yi Hao

Authors
  1. Yi Li
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  2. Yi Hao
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  3. Ming Gao
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  4. Wen Dong
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  5. Meiru Hu
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  6. Shengtao Yuan
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  7. Lun Song
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Correspondence to Lun Song.

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Yi Li, Yi Hao and Ming Gao contributed equally to this work.

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Li, Y., Hao, Y., Gao, M. et al. IKKβ downregulation is critical for triggering JNKs-dependent cell apoptotic response in the human hepatoma cells under arsenite exposure. Mol Cell Biochem 358, 61–66 (2011). https://doi.org/10.1007/s11010-011-0921-3

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  • DOI: https://doi.org/10.1007/s11010-011-0921-3

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