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

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-kappa B activation through inhibiting phosphorylation on the NF-kappa B p65 subunit and consequently the DNA binding of NF-kappa B. 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-kappa B 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)