MC37, a new mono-carbonyl curcumin analog, induces G2/M cell cycle arrest and mitochondria-mediated apoptosis in human colorectal cancer cells
MC37, a new mono-carbonyl curcumin analog, induces G2/M cell cycle arrest and mitochondria-mediated apoptosis in human colorectal cancer cells
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MC37 是一种新型单羰基姜黄素类似物，可诱导人结直肠癌细胞 G2/M 细胞周期停滞和线粒体介导的细胞凋亡
DOI：
10.1016/j.ejphar.2016.12.030
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发表时间：
2017-02-05
影响因子：
5
通讯作者：
Bu, Xianzhang
中科院分区：
文献类型：
--
作者：
Liang, Baoxia;Liu, Ziyi;Bu, Xianzhang
（E)-1-（3'-氟-[1,1'-联苯-3-基）-3-（3-羟基-4-甲氧基苯基）prop-2-en-1-one） （MC37）是一种新型的单羰基姜黄素类似物，是我们实验室先前合成的一种核因子κ B （nf - κ B）抑制剂，对几种癌细胞具有良好的细胞毒性。在本研究中，我们进一步的研究表明MC37在人类结直肠癌细胞中的生长抑制活性与细胞周期进程的阻滞和细胞凋亡的诱导有关。作为一种多靶点药物，MC37抑制细胞内微管组装，改变细胞周期蛋白依赖性激酶1 （cyclin-dependent kinase 1, CDK1）的表达，最终诱导G2/M细胞周期阻滞。MC37破坏线粒体膜电位（MMP），增加Bax/Bcl-2比值，激活caspase-9/3级联，最终导致癌细胞凋亡，提示线粒体介导的凋亡通路参与了MC37诱导的细胞凋亡。总之，这些观察结果表明，单羰基姜黄素类似物将作为多靶点先导物开发有希望的抗结直肠癌药物。
(E)-1-(3'-fluoro-[1,1'-biphenyl-3-yl)-3-(3-hydroxy-4-methoxyphenyl)prop-2-en-1-one) (MC37), a novel mono-carbonyl curcumin analog, was previously synthesized in our laboratory as a nuclear factor kappa B (NF-kappa B) inhibitor with excellent cytotoxicity against several cancer cell lines. In this study, our further investigations showed that the potent growth inhibitory activity of MC37 in human colorectal cancer cells was associated with the arrest of cell cycle progression and the induction of apoptosis. As a multi-targeted agent, MC37 inhibited the intracellular microtubule assembly, altered the expression of cyclin-dependent kinase 1 (CDK1), and ultimately induced G2/M cell cycle arrest. Moreover, MC37 collapsed the mitochondrial membrane potential (MMP), increased the Bax/Bcl-2 ratio, activated the caspase-9/3 cascade, and finally led to cancer cells apoptosis, suggesting that the mitochondrial-mediated apoptotic pathway was involved in MC37-induced apoptosis. In conclusion, these observations demonstrated that mono-carbonyl curcumin analogs would serve as multi-targeted lead for promising anti-colorectal cancer agent development.