文章基本信息

标题：Angiopoietin-like protein 4 potentiates DATS-induced inhibition of proliferation, migration, and invasion of bladder cancer EJ cells; involvement of G2/M-phase cell cycle arrest, signaling pathways, and transcription factors-mediated MMP-9 expression
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作者：Seung-Shick Shin ; Jun-Hui Song ; Byungdoo Hwang 等
期刊名称：Food & Nutrition Research
印刷版ISSN：1654-661X
出版年度：2017
语种：English
出版社：Co-Action Publishing
摘要：Background : Diallyl trisulfide (DATS), a bioactive sulfur compound in garlic, has been highlighted due to its strong anti-carcinogenic activity. Objective : The current study investigated the molecular mechanism of garlic-derived DATS in cancer cells. Additionally, we explored possible molecular markers to monitoring clinical responses to DATS-based chemotherapy. Design : EJ bladder carcinoma cells were treated with different concentration of DATS. Molecular changes including differentially expressed genes in EJ cells were examined using immunoblot, FACS cell cycle analysis, migration and invasion assays, electrophoresis mobility shift assay (EMSA) , microarray, and bioinformatics analysis. Results : DATS inhibited EJ cell growth via G 2 /M-phase cell cycle arrest. ATM-CHK2-Cdc25c-p21WAF1-Cdc2 signaling cascade, MAPKs, and AKT were associated with the DATS-mediated growth inhibition of EJ cells. DATS-induced inhibition of migration and invasion was correlated with down-regulated MMP-9 via reduced activation of AP-1, Sp-1, and NF-κB. Through microarray gene expression analysis, ANGPTL4, PLCXD1, and MMP3 were identified as candidates of molecular targets of DATS. Introduction of each gene to EJ cells revealed that ANGPTL4 was associated with the DATS-induced inhibition of cell growth, migration, and invasion. Conclusions : ANGPTL4 regulates DATS-mediated inhibition of proliferation, migration, and invasion of EJ cells, and thus, has potential as a prognostic marker for bladder cancer patients.
关键词：ANGPTL4;bladder cancer;diallyl trisulfide;migration;invasion;microarray