Inactivation of NF-κB by genistein is mediated via Akt signaling pathway in breast cancer cells
Inactivation of NF-κB by genistein is mediated via Akt signaling pathway in breast cancer cells
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DOI：
10.1038/sj.onc.1206583
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发表时间：
2003-07-24
期刊：
影响因子：
8
通讯作者：
Sarkar, FH
中科院分区：
文献类型：
--
作者：
Gong, LJ;Li, YW;Sarkar, FH
Genastein是在大豆产品中发现的一种天然异黄酮，已被认为与亚洲妇女的乳腺癌率较低有关。我们实验室和其他人的研究表明，染料木黄酮可以通过调节乳腺癌细胞中与凋亡相关的基因的表达来诱导凋亡。然而，染料木黄酮诱导凋亡细胞死亡的精确分子机制尚不清楚。为了研究这种机制，我们测试了Akt和NF-kappab在染料蛋白酶处理的MDA-MB-231乳腺癌细胞中的作用。我们发现，通过下调AKT和NF-kappab途径，抑制细胞生长和染料凋亡诱导的部分是介导的。凝胶转移测定法表明，诱导用Akt cDNA转染的MDA-MB-231细胞中的NF-kappab DNA结合活性，这表明NF-kappab和Akt信号通路之间存在串扰。此外，我们发现染料木黄酮可以消除EGF和AKT诱导的NF-kappab激活。从这些结果中，我们得出的结论是，在MDA-MB-231乳腺癌细胞中，染料碱性NF-kappab灭活是通过AKT途径介导的，这对于预防和/或治疗乳腺癌的策略的理性设计可能很有用。 。
Genistein, a natural isoflavonoid found in soybean products, has been proposed to be associated with a lower rate of breast cancer in Asian women. Studies from our laboratory and others have shown that genistein can induce apoptosis by regulating the expression of apoptosis-related genes in breast cancer cells. However, the precise molecular mechanism(s) by which genistein induces apoptotic cell death is not clear. In order to investigate such mechanism, we tested the role of Akt and NF-kappaB in genistein-treated MDA-MB-231 breast cancer cells. We found that inhibition of cell growth and induction of apoptosis by genistein are partly mediated through the downregulation of Akt and NF-kappaB pathways. Gel shift assay showed that NF-kappaB DNA-binding activity in MDA-MB-231 cells transfected with Akt cDNA was induced, suggesting that there is a cross-talk between NF-kappaB and Akt signaling pathway. Moreover, we found that genistein could abrogate EGF and Akt induced NF-kappaB activation. From these results, we conclude that the inactivation of NF-kappaB by genistein in MDA-MB-231 breast cancer cells is partly mediated via Akt pathway, which could be useful for rational design of strategies for the prevention and/or treatment of breast cancer.