title: 1-butyltryptophan inhibits cell proliferation, migration, and invasion through the Akt pathway in human gastric cancer cells.
abstract: We have previously demonstrated that novel 1-alkyl-tryptophan analogs 1-butyltryptophan (1-BT) can serve as a potential antitumor agent. However, the molecular mechanisms of 1-BT on cancer cells remain to be elucidated. The effect of 1-BT on cell proliferation was detected by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and clone formation assay in SGC7901 and AGS cells. Cell cycle was determined by flow cytometry. Cell migration and invasion was determined by wound healing assay and transwell assay. The expression of cyclin-dependent kinase 4 (CDK4), cyclin D1, p16, PCNA, phosphorylated Akt, total Akt, phosphorylated ERK1/2, and total ERK1/2 was examined using Western blotting. Our data demonstrated that 1-BT inhibited cell proliferation in a dose- and time-dependent manner by the downregulation of expression of cyclin D1 and CDK4 and by the upregulation of p16 expression. The inhibition of cell growth was also demonstrated by cell cycle arrest at the G1/S phase. Furthermore, 1-BT inhibited cell migration and invasion in SGC7901 cells. In addition, we found that phosphorylated Akt was suppressed in 1-BT treated SGC7901 cells. Overexpression of activated Akt reversed the effects of 1-BT on cell migration and invasion in SGC7901 cells. These results indicated that 1-BT inhibited gastric cancer cells proliferation and migration through the Akt pathway, which has the potential clinical significance in the prevention and treatment of gastric cancer.
authors.affiliation: Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, China, beibeisun2008@163.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Sun
authors.forename: Hua
authors.initials: H
authors.lastname: Tian
authors.forename: YangXun
authors.initials: Y
authors.lastname: Xin
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000235:genetics; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014364:Tryptophan / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D019938:Cyclin D1; C097301:tryptophan butyl ester; D014364:Tryptophan; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt