1-butyltryptophan inhibits cell proliferation, migration, and invasion through the Akt pathway in human gastric cancer cells
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.
Keywords1-butyltryptophan Gastric cancer Akt Migration Invasion
This work was supported by grants from the National Natural Science Foundation of China (81201116).
Conflicts of interest
- 1.Melton SD, Genta RM, Souza RF. Biomarkers and molecular diagnosis of gastrointestinal and pancreatic neoplasms. Nat Rev. 2010;7:620–8.Google Scholar
- 20.Ogasawara N, Oguro T, Sakabe T, Matsushima M, Takikawa O, Isobe K, et al. Hemoglobin induces the expression of indoleamine 2,3-dioxygenase in dendritic cells through the activation of pi3k, pkc, and nf-kappab and the generation of reactive oxygen species. J Cell Biochem. 2009;108:716–25.CrossRefPubMedGoogle Scholar
- 21.Koorella C, Nair JR, Murray ME, Carlson LM, Watkins SK, Lee KP. Novel regulation of cd80/cd86-induced phosphatidylinositol 3-kinase signaling by notch1 protein in interleukin-6 and indoleamine 2,3-dioxygenase production by dendritic cells. J Biol Chem. 2014;289:7747–62.CrossRefPubMedPubMedCentralGoogle Scholar