title: Sanguinarine exhibits antitumor activity via up-regulation of Fas-associated factor 1 in non-small cell lung cancer.
abstract: Lung cancer is the most common type of malignancy and one of the leading causes of cancer-related deaths in the world. Non-small cell lung carcinomas (NSCLC) account for 85% cases of lung cancer. Sanguinarine (SNG) is a benzophenanthridine alkaloid isolated from plants of the Papaveraceae family that possess diverse biological activities. SNG exhibits antitumor effects in several cancer cells. However, the effects of SAN on NSCLC proliferation, invasion, and migration and the mechanisms remain to be clarified. We showed that SNG concentration- and time-dependently decreased the cell proliferation, viability, and induced a marked increase in cell death in A549 cells. SNG inhibited invasion and migration and induced S phase cell cycle arrest and apoptosis. SNG resulted in a significant increase of E-cadherin expression and a marked decrease of the expression of N-cadherin, Vimentin, Smad2/3, and Snail and the phosphorylation of Smad2. SNG increased Fas-associated factor 1 (FAF1) expression and upregulation of FAF1 inhibited cell proliferation, invasion, and migration and induced cell cycle arrest and apoptosis in NSCLC cells. Knockdown of FAF1 suppressed SNG-induced inhibition of cell proliferation, invasion, and migration and induction of cell cycle arrest and apoptosis in NSCLC cells. SNG also inhibited implanted tumor growth and increased FAF1 expression in tumors in vivo. Our findings highlight FAF1 as a novel therapeutic target and provide a new insight in the potential use of SNG for the inhibition of NSCLC.
authors.affiliation: Department of Cardiothoracic Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, 435000, People's Republic of China.
authors.forename: Guangxia
authors.initials: G
authors.lastname: Wei
authors.affiliation: Department of Cardiothoracic Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, 435000, People's Republic of China.
authors.forename: Yahuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Cardiothoracic Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, 435000, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.affiliation: Department of Cardiothoracic Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, 435000, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Cardiothoracic Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, 435000, People's Republic of China.
authors.forename: Zhengjun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiothoracic Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, 435000, People's Republic of China.
authors.forename: Zhanwen
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000072283:A549 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D053119:Benzophenanthridines / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D053119:Benzophenanthridines; C490780:FAF1 protein, human; D007546:Isoquinolines; D009363:Neoplasm Proteins; C005705:sanguinarine
keywords: Fas-associated factor 1; cell proliferation; invasion; migration; non-small cell lung carcinomas; sanguinarine