title: Sanguinarine inhibits growth and invasion of gastric cancer cells via regulation of the DUSP4/ERK pathway.
abstract: Sanguinarine, a bioactive benzophenanthridine alkaloid extracted from plants of the Papaveraceae family, has shown antitumour effects in multiple cancer cells. But the therapeutic effects and regulatory mechanisms of sanguinatine in gastric cancer (GC) remain elusive. This study was aimed to investigate the correlation of dual-specificity phosphatase 4 (DUSP4) expression with clinicopathologic features and overall survival in patients with GC and explore the effects of sanguinarine on tumour growth and invasion in GC cells (SGC-7901 and HGC-27) and underlying molecular mechanisms. Immunohistochemical analysis showed that decreased DUSP4 expression was associated with the sex, tumour size, depth of invasion and distant metastasis in patients with GC. Functional experiments including CCK-8, Transwell and flow cytometry analysis indicated that sanguinarine or DUSP4 overexpression inhibited GC cell viability and invasive potential, and induced cell apoptosis and cycle arrest in S phase, but DUSP4 knockdown attenuated the antitumour activity of sanguinarine. Further observation demonstrated that sanguinarine up-regulated the expression of DUSP4 and Bcl-2-associated X protein (Bax), but down-regulated phosphorylated extracellular signal-regulated kinase (p-ERK), proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP-2) and B-cell lymphoma 2 (Bcl-2) expression. Taken together, our findings indicate that sanguinarine inhibits growth and invasion of GC cells through regulation of the DUSP4/ERK pathway, suggesting that sanguinarine may have potential for use in GC treatment.
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.
authors.forename: Yun-Min
authors.initials: YM
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Da
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.
authors.forename: Jin-Shui
authors.initials: JS
authors.lastname: Zhu
mesh_terms: D000368:Aged; D053119:Benzophenanthridines / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D054637:Dual-Specificity Phosphatases / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D053119:Benzophenanthridines; D007546:Isoquinolines; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C005705:sanguinarine; D054639:Mitogen-Activated Protein Kinase Phosphatases; C490583:DUSP4 protein, human; D054637:Dual-Specificity Phosphatases
keywords: Sanguinarine; dual-specificity phosphatase 4; extracellular signal-regulated kinase; gastric cancer; invasion; proliferation