The dietary flavonoid apigenin sensitizes malignant tumor cells to tumor necrosis factor-related apoptosis-inducing ligand
The dietary flavonoid apigenin sensitizes malignant tumor cells to tumor necrosis factor-related apoptosis-inducing ligand
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DOI：
10.1158/1535-7163.mct-05-0431
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发表时间：
2006-04-01
影响因子：
5.7
通讯作者：
Sakai, T
中科院分区：
文献类型：
--
作者：
Horinaka, M;Yoshida, T;Sakai, T
芹菜素类黄酮具有预防和治疗恶性肿瘤的潜力。在这份报告中，我们首次表明，芹菜素显着诱导死亡受体5（DR 5）的表达，并协同作用与外源性可溶性重组人肿瘤坏死因子相关凋亡诱导配体（TRAIL）诱导恶性肿瘤细胞凋亡。由于其选择性诱导癌细胞凋亡的能力，TRAIL是癌症治疗的有希望的候选者。芹菜素和TRAIL在次优浓度下的组合使用诱导Bcl-2相互作用结构域切割和半胱天冬酶-8、-10、-9和-3的活化。此外，人重组DR 5/Fc嵌合蛋白和半胱天冬酶抑制剂显着抑制细胞凋亡诱导！通过芹菜素和TRAIL的结合。另一方面，芹菜素介导的DR 5表达的诱导在正常人外周血单核细胞中未观察到。此外，芹菜素不敏感的正常人外周血单核细胞TRAIL诱导的凋亡。这些结果表明，芹菜素和TRAIL的这种联合治疗可能是有希望的，作为一种新的治疗恶性肿瘤。
Dietary flavonoid apigenin is expected to have preventive and therapeutic potential against malignant tumors. In this report, we show for the first time that apigenin markedly induces the expression of death receptor 5 (DR5) and synergistically acts with exogenous soluble recombinant human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to induce apoptosis in malignant tumor cells. TRAIL is a promising candidate for cancer therapeutics due to its ability to selectively induce apoptosis in cancer cells. The combined use of apigenin and TRAIL at suboptimal concentrations induces Bcl-2-interacting domain cleavage and the activation of caspases-8, -10, -9, and -3. Furthermore, human recombinant DR5/Fc chimera protein and caspase inhibitors dramatically inhibit apoptosis induces! by the combination of apigenin and TRAIL. On the other hand, apigenin-mediated induction of DR5 expression is not observed in normal human peripheral blood mononuclear cells. Moreover, apigenin does not sensitize normal human peripheral blood mononuclear cells to TRAIL-induced apoptosis. These results suggest that this combined treatment with apigenin and TRAIL might be promising as a new therapy against malignant tumors.