Kaempferol Induces Apoptosis in Two Different Cell Lines Via Akt Inactivation, Bax and SIRT3 Activation, and Mitochondrial Dysfunction
Kaempferol Induces Apoptosis in Two Different Cell Lines Via Akt Inactivation, Bax and SIRT3 Activation, and Mitochondrial Dysfunction
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DOI：
10.1002/jcb.22044
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发表时间：
2009-03-01
影响因子：
4
通讯作者：
Russo, Matteo Antonio
中科院分区：
文献类型：
--
作者：
Marfe, Gabriella;Tafani, Marco;Russo, Matteo Antonio
山奈酚(3，4‘，5，7-四羟基黄酮)是一种存在于多种天然来源的黄酮类化合物，具有抗氧化和促氧化活性。山奈酚已被证明具有通过诱导细胞凋亡程序的抗癌特性。本文报道50亩山奈酚作用于慢性粒细胞白血病细胞系KG62和早幼粒细胞白血病U937，引起抗氧化酶锰和铜/锌超氧化物歧化酶(SOD)的升高。山奈酚可通过下调Bcl2的表达和上调Bax的表达来诱导细胞凋亡。诱导线粒体释放细胞色素c进入胞浆，并显著激活caspase-3、-9和PARP裂解。山奈酚处理增加了NAD依赖的脱乙酰酶SIRT3的表达和线粒体定位。稳定高表达SIRT3的K562细胞对山奈酚更为敏感，而沉默SIRT3并不增加K562细胞对山奈酚的耐药性。山奈酚对K562和U937细胞的PI3K活性和Akt在Ser473和Thr308的去磷酸化也有抑制作用。总之，我们的研究表明，山奈酚诱导的K562和U937细胞株的氧化应激导致Akt失活，线粒体阶段的凋亡程序激活，Bax和SIRT3的表达增加，Bcl-2的表达减少，细胞色素c的释放，caspase-3的激活，细胞死亡。J.细胞。生物化学。106：643-650,2009。(C)2009年Wiley-Liss，Inc.
Kaempferol (3,4',5,7-tetrahydroxyflavone) is a flavonoid with anti- and pro-oxidant activity present in various natural sources. Kaempferol has been shown to posses anticancer properties through the induction of the apoptotic program. Here we report that treatment of the chronic myelogenous leukemia cell line KG62 and promyelocitic human leukemia U937 with 50 mu M kaempferol resulted in an increase of the antioxidant enzymes Mn and Cu/Zn superoxide dismutase (SOD). Kaempferol treatment induced apoptosis by decreasing the expression of Bcl-2 and increasing the expressions of Bax. There were also induction of mitochondrial release of cytochrome c into cytosol and significant activation of caspase-3, and -9 with PARP cleavage. Kaempferol treatment increased the expression and the mitochondria localization of the NAD-dependent deacetylase SIRT3. K562 cells stably overexpressing SIRT3 were more sensitive to kaempferol, whereas SIRT3 silencing did not increase the resistance or K562 cells to kaempferol. Inhibition of PI3K and de-phosphorylation of Akt at Ser473 and Thr308 was also observed after treating both K562 and U937 cells with kaempferol. In conclusion our study shows that the oxidative stress induced by kaempferol in K562 and U937 cell lines causes the inactivation of Akt and the activation of the mitochondrial phase of the apoptotic program with an increase of Bax and SIRT3, decrease of Bcl-2, release of cytochrome c, caspase-3 activation, and cell death. J. Cell. Biochem. 106: 643-650, 2009. (C) 2009 Wiley-Liss, Inc.