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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• 作者：Baoxia Liang^a ; Ziyi Liu^a ; Yingnan Cao^b ; Cuige Zhu^a ; Yinglin Zuo^a ; Lei Huang^a ; Gesi Wen^a ; Nana Shang^a ; Yu Chen^a ; Xin Yue^a ; Jun Du^a ; Baojian Li^c ; Binhua Zhou^a ; ^{sichuang1984@outlook.com} ; Xianzhang Bu^a ; ^{phsbxzh@mail.sysu.edu.cn}
• 关键词：NF-κB ; nuclear factor kaapa B ; CDK1 ; cyclin-dependent kinase 1 ; MMP ; mitochondrial membrane potential ; CRC ; colorectal cancer ; DMEM ; Dulbecco's modified Eagle's medium ; PMSF ; phenylmethylsulfonylfluoride ; S.D. ; standard deviation ; PARP ; poly-ADP Ribose polymerase ; SRB ; sulforhodamine B ; TNF-α ; tumor necrosis factor alpha ; DMSO ; dimethyl sulfoxide ; COX-2 ; cyclooxygenase 2 ; FBS ; fetal bovine serum ; VEGF ; vascular endothelial growth factor ; TCA ; trichloroacetic acid ; IL-6 ; interleukin 6 ; SDS-PAGE
• 刊名：European Journal of Pharmacology
• 出版年：2017
• 出版时间：5 February 2017
• 年：2017
• 卷：796
• 期：Complete
• 页码：139-148
• 全文大小：1231 K
• 卷排序：796

文摘

(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-κB) 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.