Luteolin induces apoptosis via death receptor 5 upregulation in human malignant tumor cells
Luteolin induces apoptosis via death receptor 5 upregulation in human malignant tumor cells
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DOI：
10.1038/sj.onc.1208874
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发表时间：
2005-11-03
期刊：
影响因子：
8
通讯作者：
Sakai, T
中科院分区：
文献类型：
--
作者：
Horinaka, M;Yoshida, T;Sakai, T
木犀草素是一种天然存在的类黄酮，可诱导多种癌细胞凋亡。然而，很少有人知道有关的分子机制负责这一活动。在这份报告中，我们揭示了一种新的机制，其中毛地黄黄酮诱导的细胞凋亡发生，并首次表明，由毛地黄黄酮的细胞凋亡是通过死亡受体5（DR 5）上调介导的。木犀草素可显著诱导DR 5的表达，沿着Bcl-2相互作用结构域的切割和caspase-8、-10、-9和-3的激活。此外，用siRNA抑制DR 5表达有效地减少了木犀草素诱导的半胱天冬酶活化和凋亡。人重组DR 5/Fc也抑制木犀草素诱导的细胞凋亡。另一方面，毛地黄黄酮既不诱导DR 5蛋白表达，也不诱导正常人外周血单个核细胞凋亡。这些结果表明，由毛地黄黄酮诱导的DR 5在毛地黄黄酮诱导的细胞凋亡中起作用，并提出了用毛地黄黄酮治疗可能有希望作为一种新的治疗癌症的可能性。
Luteolin, a naturally occurring flavonoid, induces apoptosis in various cancer cells. Little is known however concerning the underlying molecular mechanisms responsible for this activity. In this report, we reveal a novel mechanism by which luteolin-induced apoptosis occurs, and show for the first time that the apoptosis by luteolin is mediated through death receptor 5 (DR5) upregulation. Luteolin markedly induced the expression of DR5, along with Bcl-2-interacting domain cleavage and the activation of caspase-8, -10, -9 and -3. In addition, suppression of DR5 expression with siRNA efficiently reduced luteolin-induced caspase activation and apoptosis. Human recombinant DR5/Fc also inhibited luteolin-induced apoptosis. On the other hand, luteolin induced neither DR5 protein expression nor apoptosis in normal human peripheral blood mononuclear cells. These results suggest that DR5 induced by luteolin plays a role in luteolin-induced apoptosis, and raises the possibility that treatment with luteolin might be promising as a new therapy against cancer.