(E)-2,4-Bis(p-hydroxyphenyl)-2-butenal inhibits tumor growth via suppression of NF-κB and induction of death receptor 6
(E)-2,4-Bis(p-hydroxyphenyl)-2-butenal inhibits tumor growth via suppression of NF-κB and induction of death receptor 6
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DOI：
10.1007/s10495-013-0903-x
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发表时间：
2014-01-01
期刊：
影响因子：
7.2
通讯作者：
Hong, Jin Tae
中科院分区：
文献类型：
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作者：
Ban, Jung Ok;Jung, Young-Suk;Hong, Jin Tae
已知美拉德反应产物在化学预防中有效。在这里，我们重点研究了 (E)-2,4-双(对羟基苯基)-2-丁烯醛对体外和体内结肠癌的抗癌作用。我们通过细胞周期和细胞凋亡分析分析了(E)-2,4-双(对羟基苯基)-2-丁烯醛对结肠癌细胞的抗癌活性。阐明其作用机制、NF-kappa B DNA结合活性、对接模型以及pull-down实验。此外，还研究了结肠癌的异种移植模型以测试(E)-2,4-双(对羟基苯基)-2-丁烯醛的体内作用。 (E)-2,4-双(对羟基苯基)-2-丁烯醛抑制结肠癌细胞（SW620 和 HCT116）生长，随后通过下调 NF-κ B 活性以浓度依赖性方式诱导细胞凋亡。在对接模型和下拉实验中，(E)-2,4-双(对羟基苯基)-2-丁烯醛直接与 IKK β 的三个氨基酸残基结合，从而除了诱导死亡受体 6 (DR6) 及其靶凋亡基因外，还抑制 IKK β 活性。最后，(E)-2,4-双(对羟基苯基)-2-丁烯醛通过抑制 IKK beta/NF-κ B 活性和 DR6 过表达来抑制贴壁依赖性癌细胞生长，以及异种移植模型中伴随细胞凋亡的肿瘤生长。这些结果表明，(E)-2,4-双(对羟基苯基)-2-丁烯醛通过抑制 IKK beta/NF-κ B 活性和诱导 DR6 表达来抑制结肠癌细胞生长。
The Maillard reaction products are known to be effective in chemoprevention. Here, we focused on the anti-cancer effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal on in vitro and in vivo colon cancer. We analysed the anti-cancer activity of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal on colon cancer cells by using cell cycle and apoptosis analysis. To elucidate it's mechanism, NF-kappa B DNA binding activity, docking model as well as pull-down assay. Further, a xenograft model of colon cancer was studied to test the in vivo effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal. (E)-2,4-Bis(p-hydroxyphenyl)-2-butenal inhibited colon cancer cells (SW620 and HCT116) growth followed by induction of apoptosis in a concentration-dependent manner via down-regulation of NF-kappa B activity. In docking model as well as pull-down assay, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal directly binds to three amino acid residues of IKK beta, thereby inhibited IKK beta activity in addition to induction of death receptor 6 (DR6) as well as their target apoptotic genes. Finally, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal suppressed anchorage-independent cancer cell growth, and tumor growth in xenograft model accompanied with apoptosis through inhibition of IKK beta/NF-kappa B activity, and overexpression of DR6. These results suggest that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal inhibits colon cancer cell growth through inhibition of IKK beta/NF-kappa B activity and induction of DR6 expression.