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.
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.
Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China.
Lan
L
Yang
Xue L
XL
Zheng
Hong
H
Sun
Ying J
YJ
Zhong
Qiong
Q
Wang
Hai N
HN
He
Xun W
XW
Shi
Bing
B
Zhou
Jin K
JK
Li
Yong
Y
Lin
Lin
L
Zhang
Xia
X
Wang
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002374:Catalase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D004365:Drugs, Chinese Herbal; D024202:Electrophoretic Mobility Shift Assay; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016877:Oxidants / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004365:Drugs, Chinese Herbal; D044950:Flavanones; D016328:NF-kappa B; D016877:Oxidants; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D002374:Catalase; D008156:Luciferases; C085514:wogonin