Catalase suppression-mediated H(2)O(2) accumulation in cancer cells by wogonin effectively blocks tumor necrosis factor-induced NF-κB activation and sensitizes apoptosis

Cancer Sci. 2011 Apr;102(4):870-6. doi: 10.1111/j.1349-7006.2011.01874.x. Epub 2011 Feb 24.

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 (H(2)O(2)). 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 H(2)O(2). Thus, wogonin specifically sensitizes cancer cells to TNF-induced cytotoxicity through H(2)O(2)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Catalase / antagonists & inhibitors*
  • Catalase / metabolism
  • Cell Line, Tumor
  • Drugs, Chinese Herbal
  • Electrophoretic Mobility Shift Assay
  • Flavanones / pharmacology*
  • Humans
  • Hydrogen Peroxide / metabolism*
  • Luciferases / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Oxidants / metabolism
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Drugs, Chinese Herbal
  • Flavanones
  • NF-kappa B
  • Oxidants
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Hydrogen Peroxide
  • Catalase
  • Luciferases
  • wogonin