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Inhibition of heme oxygenase-1 enhances anti-cancer effects of arsenic trioxide on glioma cells

  • Laboratory Investigation - Human/Animal Tissue
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Abstract

We have previously reported that arsenic trioxide (ATO) could inhibit glioma growth both in vitro and in vivo, and demonstrated its potent therapeutic effects on gliomas. In this study we showed that ATO induced cell damage and heme oxygenase-1 (HO-1) expression in glioma cells via ROS generation. HO-1 inducer clearly protected from ATO-induced cell death and ROS generation, and HO-1 inhibitor led to a significant increase in cell death and ROS generation induced by ATO. In addition, knockdown of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) strongly inhibited HO-1 expression induced by ATO, and significantly enhanced ATO-induced oxidative damage. Our results demonstrated, for the first time, that HO-1 inhibition or Nrf2 knockdown significantly potentiated ATO’s effects on glioma cells. Considering that HO-1 is highly expressed in glioma tissues, administration of ATO in combination with either HO-1 inhibitor or Nrf2 knockdown may act as a new approach to the treatment of glioma.

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Acknowledgments

This study was supported by the Special Prophase Project of National Basic Research Program of China (2009cb526404 to ZS), the National Natural Science Foundations of China (30901533 to LY and 30772239 to ZS), and the Foundation of the Harbin Science and Technology Committee (2007AA3CS083-2 to ZS).

Declaration

This study has no commercial interest. No financial or material support was received from any commercial source which is directly or indirectly related to the scientific work.

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Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, The People’s Republic of China

    Yaohua Liu, Yuan Liang, Guang Yang, Xu Zhang, Zhe Sun, Changbin Shi & Shiguang Zhao

  2. Institute of Brain Science, Harbin Medical University, Harbin, Heilongjiang, The People’s Republic of China

    Yaohua Liu, Yuan Liang, Guang Yang, Xu Zhang, Zhe Sun, Changbin Shi & Shiguang Zhao

  3. Department of Biochemistry, Harbin Medical University, Harbin, Heilongjiang, The People’s Republic of China

    Tianhu Zheng

  4. Section of Neurosurgery, Department of Surgery, The University of Chicago Medical Center and Pritzker School of Medicine, 5841 South Maryland Avenue (MC 3026), Chicago, IL, 60637, USA

    Changbin Shi

Authors
  1. Yaohua Liu
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  2. Yuan Liang
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  3. Tianhu Zheng
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  4. Guang Yang
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  5. Xu Zhang
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  6. Zhe Sun
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  7. Changbin Shi
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  8. Shiguang Zhao
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Corresponding author

Correspondence to Shiguang Zhao.

Additional information

Yaohua Liu and Yuan Liang contributed equally to this work.

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Liu, Y., Liang, Y., Zheng, T. et al. Inhibition of heme oxygenase-1 enhances anti-cancer effects of arsenic trioxide on glioma cells. J Neurooncol 104, 449–458 (2011). https://doi.org/10.1007/s11060-010-0513-1

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  • DOI: https://doi.org/10.1007/s11060-010-0513-1

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