Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China.
Cancer Sci. 2011 Apr;102(4):870-6. doi: 10.1111/j.1349-7006.2011.01874.x. Epub 2011 Feb 24.
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.
已经付出了巨大的努力来提高肿瘤坏死因子（TNF）的抗癌价值。在这项研究中，我们表明，从黄芩（黄芩）中分离出的黄酮类化合物汉黄芩素协同增强了源自宫颈、卵巢和肺的癌细胞对 TNF 诱导的细胞凋亡的敏感性，这与过氧化氢酶活性的抑制和细胞内过氧化氢（H2O2）的增加有关。汉黄芩素诱导的活性氧通过抑制 NF-κB p65 亚基的磷酸化并进而抑制 NF-κB 的 DNA 结合来阻断 TNF 诱导的 NF-κB 激活。此外，汉黄芩素抑制了抗凋亡因子 c-FLIP 的表达，这伴随着 TNF 诱导的半胱天冬酶 8 激活的增强，从而引发凋亡。重要的是，汉黄芩素不会使正常的支气管上皮细胞对 TNF 诱导的细胞死亡敏感，这与 H2O2 的诱导缺陷有关。因此，汉黄芩素通过 H2O2 介导的 NF-κB 抑制和凋亡激活特异性增强癌细胞对 TNF 诱导的细胞毒性。我们的数据为汉黄芩素抗癌活性的分子机制提供了重要的见解，并表明这种常见的类黄酮可作为癌症治疗的 TNF 佐剂。
