Premium
Regulation of Notch Signaling Pathway by Diallyl Trisulfide in Pancreatic Cancer Cells
Author(s) -
Stan Silvia D.,
Du Yanyan
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb352
Subject(s) - notch signaling pathway , pancreatic cancer , diallyl trisulfide , cancer research , signal transduction , chemistry , microbiology and biotechnology , cancer , biology , apoptosis , medicine , biochemistry
Notch signaling pathway plays a key role in the development and progression of pancreatic cancer. The low survival of pancreatic cancer patients is often attributed to metastatic disease due to late diagnosis. In the canonical Notch signaling pathway, binding of the Notch ligands ( e.g. , Jagged‐1, Jagged‐2) to the Notch receptors leads to activation of Notch signaling pathway and causes an invasive tumor phenotype. The aim of this study was to determine the effect of diallyl trisulfide (DATS), a bioactive compound from Allium vegetables, on regulation of Notch signaling pathway in pancreatic cancer cells. We analyzed the expression of Notch receptors and ligands upon exposure to DATS in pancreatic cancer cells. Here we report, for the first time, that DATS downregulates Notch ligand Jagged‐1 in AsPC1 and MIAPaca2 pancreatic cancer cells. Ectopic expression of Jagged‐1 showed that DATS induces Jagged‐1‐dependend apoptosis in AsPC1 cells. Dose‐dependent inhibition of Jagged 2 was observed upon exposure to DATS in MIAPaca2 cells. Treatment with DATS resulted in downregulation of Notch‐1 receptor. In addition, DATS treatment induced a dose‐dependent inhibition of ADAM‐17, protease involved in cleavage of the extracellular domain of the Notch receptor. In summary, the results of this study show that DATS targets Notch pathway components overexpressed in pancreatic cancer, and supports further investigation of DATS as a potential chemopreventive agent for pancreatic cancer. (This work was supported in part by a Showalter Research Trust award to SDS.)