• Open Access

Catalase suppression-mediated H2O2 accumulation in cancer cells by wogonin effectively blocks tumor necrosis factor-induced NF-κB activation and sensitizes apoptosis

Authors

  • Lan Yang,

    1. Department of Forensic Biology, West China School of Preclinical and Forensic Medicine
    2. Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children’s Health, West China Second University Hospital
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  • Xue L. Zheng,

    1. Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children’s Health, West China Second University Hospital
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  • Hong Sun,

    1. Department of Forensic Biology, West China School of Preclinical and Forensic Medicine
    2. Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children’s Health, West China Second University Hospital
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  • Ying J. Zhong,

    1. Department of Forensic Analytical Toxicology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China
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  • Qiong Wang,

    1. Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children’s Health, West China Second University Hospital
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  • Hai N. He,

    1. Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children’s Health, West China Second University Hospital
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  • Xun W. Shi,

    1. Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children’s Health, West China Second University Hospital
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  • Bing Zhou,

    1. Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children’s Health, West China Second University Hospital
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  • Jin K. Li,

    1. Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children’s Health, West China Second University Hospital
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  • Yong Lin,

    1. Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children’s Health, West China Second University Hospital
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  • Lin Zhang,

    Corresponding author
    1. Department of Forensic Biology, West China School of Preclinical and Forensic Medicine
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  • Xia Wang

    Corresponding author
    1. Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children’s Health, West China Second University Hospital
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To whom correspondence should be addressed.
E-mail: xiawang@scu.edu.cn; zhanglin@scu.edu.cn

Abstract

Tremendous effort has been made to improve the anticancer value of tumor necrosis factor (TNF). In this study, we show that wogonin, a flavonoid isolated from Huang-Qin (Scutellaria baicalensis), synergistically sensitizes cancer cells derived from the cervix, ovary and lung to TNF-induced apoptosis, which was associated with inhibition of catalase activity and an increase of cellular hydrogen peroxide (H2O2). Wogonin-induced reactive oxygen species block TNF-induced NF-κB activation through inhibiting phosphorylation on the NF-κB p65 subunit and consequently the DNA binding of NF-κB. In addition, wogonin suppressed the expression of the antiapoptotic factor c-FLIP, which is accompanied with potentiation of TNF-induced caspase 8 activation that initiates apoptosis. Importantly, wogonin did not sensitize normal bronchial epithelial cells to TNF-induced cell death, which was associated with the defect in induction of H2O2. Thus, wogonin specifically sensitizes cancer cells to TNF-induced cytotoxicity through H2O2-mediated NF-κB suppression and apoptosis activation. Our data provide important insights into the molecular mechanism underlying wogonin’s anticancer activity, and suggest this common flavonoid could be used as a TNF adjuvant for cancer therapy. (Cancer Sci 2011; 102: 870–876)

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