The combination of TRAIL and luteolin enhances apoptosis in human cervical cancer HeLa cells
The combination of TRAIL and luteolin enhances apoptosis in human cervical cancer HeLa cells
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DOI：
10.1016/j.bbrc.2005.05.179
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发表时间：
2005-08-05
影响因子：
3.1
通讯作者：
Sakai, T
中科院分区：
文献类型：
--
作者：
Horinaka, M;Yoshida, T;Sakai, T
肿瘤坏死因子相关的凋亡诱导配体(TRAIL)是肿瘤治疗领域最有前途的候选分子之一。然而，一些肿瘤细胞对TRAIL诱导的细胞凋亡具有抵抗力。我们以前的研究表明，木犀草素是一种天然存在的黄酮类化合物，它可以诱导TRAIL的受体死亡受体5(DR5)表达上调。在这里，我们首次展示了木犀草素与外源可溶性重组人TRAIL协同作用，诱导HeLa细胞凋亡，但不诱导正常人外周血单核细胞凋亡。联合使用木犀草素和TRAIL可诱导Bid的切割和caspase-8的激活。此外，人重组DR5/Fc嵌合体蛋白、caspase抑制剂和DR5 siRNA有效地减少了木犀草素和TRAIL共同处理所诱导的细胞凋亡。这些结果增加了木犀草素和TRAIL联合治疗作为一种新的癌症治疗方法的可能性。(C)2005 Elsevier Inc.保留所有权利。
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the most promising candidates for cancer therapeutics. However, some tumor cells are resistant to TRAIL-induced apoptosis. Our previous studies have shown that luteolin, a naturally occurring flavonoid, induces the up-regulation of death receptor 5 (DR5), which is a receptor for TRAIL. Here, we show for the first time that luteolin synergistically acts with exogenous soluble recombinant human TRAIL to induce apoptosis in HeLa cells, but not in normal human peripheral blood mononuclear cells. The combined use of luteolin and TRAIL induced Bid cleavage and the activation of caspase-8. Also, human recombinant DR5/Fc chimera protein, caspase inhibitors, and DR5 siRNA efficiently reduced apoptosis induced by co-treatment with luteolin and TRAIL. These results raise the possibility that this combined treatment with luteolin and TRAIL might be promising as a new therapy against cancer. (c) 2005 Elsevier Inc. All rights reserved.