β-Lapachone induces programmed necrosis through the RIP1-PARP-AIF-dependent pathway in human hepatocellular carcinoma SK-Hep1 cells.
β-Lapachone induces programmed necrosis through the RIP1-PARP-AIF-dependent pathway in human hepatocellular carcinoma SK-Hep1 cells.
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DOI：
10.1038/cddis.2014.202
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发表时间：
2014-05-15
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
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β-Lapachone激活多种细胞死亡机制，包括癌细胞的凋亡、自噬和坏死性细胞死亡。在本研究中，我们研究了β-拉帕酮诱导人肝细胞癌SK-Hep 1细胞死亡及其机制。β-拉帕酮可显著诱导细胞死亡，而不激活半胱氨酸天冬氨酸酶。β-Lapachone增加PI摄取和HMGB-1释放到细胞外间隙，这是坏死细胞死亡的标志。Necrostatin-1(RIP1激酶抑制剂)可显著抑制β-雷帕酮诱导的细胞死亡和HMGB-1的释放。此外，β-拉帕酮激活多聚腺苷二磷酸核糖聚合酶-1(PARP-1)并促进AIF的释放，而DPQ(PARP-1特异性抑制剂)或AIF siRNA可阻断β-拉帕酮诱导的细胞死亡。此外，Necrostatin-1还可阻断PARP-1的激活和胞浆AIF的转位。我们还发现β-拉帕酮诱导的ROS的产生在RIP1PARP1AIF途径的激活中起着重要作用。NQO-1抑制剂双香豆酚可抑制β-拉帕酮诱导的细胞死亡，并且NQO-1的表达与β-拉帕酮的敏感性相关。综上所述，我们的结果表明，β-雷帕酮通过依赖ROS介导的RIP1PARP1AIF途径诱导程序性坏死。
β-Lapachone activates multiple cell death mechanisms including apoptosis, autophagy and necrotic cell death in cancer cells. In this study, we investigated β-lapachone-induced cell death and the underlying mechanisms in human hepatocellular carcinoma SK-Hep1 cells. β-Lapachone markedly induced cell death without caspase activation. β-Lapachone increased PI uptake and HMGB-1 release to extracellular space, which are markers of necrotic cell death. Necrostatin-1 (a RIP1 kinase inhibitor) markedly inhibited β-lapachone-induced cell death and HMGB-1 release. In addition, β-lapachone activated poly (ADP-ribosyl) polymerase-1(PARP-1) and promoted AIF release, and DPQ (a PARP-1 specific inhibitor) or AIF siRNA blocked β-lapachone-induced cell death. Furthermore, necrostatin-1 blocked PARP-1 activation and cytosolic AIF translocation. We also found that β-lapachone-induced reactive oxygen species (ROS) production has an important role in the activation of the RIP1-PARP1-AIF pathway. Finally, β-lapachone-induced cell death was inhibited by dicoumarol (a NQO-1 inhibitor), and NQO1 expression was correlated with sensitivity to β-lapachone. Taken together, our results demonstrate that β-lapachone induces programmed necrosis through the NQO1-dependent ROS-mediated RIP1-PARP1-AIF pathway.
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过氧化氢酶消除了NQO1阳性乳腺癌中的β-拉帕酮诱导的PARP1过度激活导向的坏死。
影响因子：
5.7
作者：
Bey EA;Reinicke KE;Srougi MC;Varnes M;Anderson VE;Pink JJ;Li LS;Patel M;Cao L;Moore Z;Rommel A;Boatman M;Lewis C;Euhus DM;Bornmann WG;Buchsbaum DJ;Spitz DR;Gao J;Boothman DA
通讯作者：
Boothman DA
影响因子：
5.8
作者：
Chiu, Ling-Ya;Ho, Feng-Ming;Lin, Wan-Wan
通讯作者：
Lin, Wan-Wan
影响因子：
5.8
作者：
CRESTEIL, T;JAISWAL, AK
通讯作者：
JAISWAL, AK
影响因子：
3.7
作者：
Planchon, SM;Pink, JJ;Boothman, DA
通讯作者：
Boothman, DA
影响因子：
5.3
作者：
Shen, HM;Lin, Y;Liu, ZG
通讯作者：
Liu, ZG