title: W346 inhibits cell growth, invasion, induces cycle arrest and potentiates apoptosis in human gastric cancer cells in vitro through the NF-κB signaling pathway.
abstract: The therapeutic agent selectively killing cancer cells is urgently needed for gastric cancer treatment. Curcumin has been investigated for its effect on the cancer treatment because of its significant therapeutic potential and safety profile. A synthetic unsymmetry mono-carbonyl compound termed W346 was developed from curcumin. In this study, we investigated the potential antineoplastic effect and mechanism of W346 against human gastric cancer cells. W346 suppressed the proliferation and invasion, blocked cell cycle arrest at G2/M phase, and increased apoptosis in gastric cancer cells, and it presented obviously improved anticancer activity than curcumin. Moreover, W346 effectively inhibited tumor necrosis factor (TNF-α)-induced NF-κB activation by suppressing IKK phosphorylation, inhibiting IκB-α degradation, and restraining the accumulation of NF-κB subunit p65 nuclear translocation. W346 also affected NF-κB-regulated downstream products involved in cycle arrest and apoptosis. In a word, W346 exhibited significantly improved anti-gastric cancer activity over curcumin by targeting NF-κB signaling pathway, and it is likely to be a promising starting point for the development of curcumin-based therapeutic agent.
authors.affiliation: Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.|Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.|Pharmacy Department, Tonglu First People's Hospital, Hangzhou, Zhejiang, 311500, China.
authors.forename: Bixia
authors.initials: B
authors.lastname: Weng
authors.affiliation: Institute of Sports Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Zhankun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.|Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Yanting
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Lingyi
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of General Surgery, The fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, China.
authors.forename: Guanqun
authors.initials: G
authors.lastname: Huang
authors.affiliation: Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Shilong
authors.initials: S
authors.lastname: Ying
authors.affiliation: Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.|Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.|Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Qiuxiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China. jinrongjrjr@163.com.|Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. jinrongjrjr@163.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Jin
authors.affiliation: Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. wjzwzmu@163.com.
authors.forename: Jianzhang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry; D003517:Cyclopentanes / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051996:Transcription Factor RelA / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C000614105:2-(3,4-dimethoxybenzylidene)-5-(4-hydroxy-3-methoxybenzylidene)cyclopentanone; D003517:Cyclopentanes; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C498143:RELA protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D051550:I-kappa B Kinase; D003474:Curcumin
keywords: Anticancer drug; Apoptosis; Curcumin; Gastric cancer; NF-κB; W346