title: MC37, a new mono-carbonyl curcumin analog, induces G2/M cell cycle arrest and mitochondria-mediated apoptosis in human colorectal cancer cells.
abstract: (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.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Baoxia
authors.initials: B
authors.lastname: Liang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Xinhua College of Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Yingnan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Cuige
authors.initials: C
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Gesi
authors.initials: G
authors.lastname: Wen
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Nana
authors.initials: N
authors.lastname: Shang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yue
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Du
authors.affiliation: Shenzhen Davoos tech. Ltd.Co., Room A611, Silver star tech. building, 1301 Guanguang Road, Guanlan, Longhua District, Shenzhen, PR China.
authors.forename: Baojian
authors.initials: B
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China. Electronic address: sichuang1984@outlook.com.
authors.forename: Binhua
authors.initials: B
authors.lastname: Zhou
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China. Electronic address: phsbxzh@mail.sysu.edu.cn.
authors.forename: Xianzhang
authors.initials: X
authors.lastname: Bu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology*; D003474:Curcumin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011407:Propane / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
chemical_list: C000617793:(E)-1-(3'-fluoro-(1,1'-biphenyl-3-yl)-3-(3-hydroxy-4-methoxyphenyl)prop-2-en-1-one); D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3; D053453:Caspase 9; D003474:Curcumin; D011407:Propane
keywords: Apoptosis; Cell cycle arrest; Colorectal cancer; Curcumin analogs; Microtubule assembly