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Identification of potential targets for diallyl disulfide in human gastric cancer MGC-803 cells using proteomics approaches.

Abstract
Diallyl disulfide (DADS) is characterized as an effective agent for the prevention and therapy of cancer, however, mechanisms regarding its anticancer effects are not fully clarified. In the present study, we compared the protein expression profile of gastric cancer MGC-803 cells subjected to DADS treatment with that of untreated control cells to explore potential molecules regulated by DADS. Using proteomic approaches, we identified 23 proteins showing statistically significant differences in expression, including 9 upregulated and 14 downregulated proteins. RT-PCR and western blot analysis confirmed that retinoid-related orphan nuclear receptor α (RORα) and nM23 were increased by DADS, whereas LIM kinase-1 (LIMK1), urokinase-type plasminogen activator receptor (uPAR) and cyclin-dependent kinase-1 (CDK1) were decreased. DADS treatment and knockdown of uPAR caused suppression of ERK/Fra-1 pathway, downregulation of urokinase-type plasminogen activator (uPA), matrix metalloproteinase-9 (MMP-9) and vimentin, and upregulation of tissue inhibitor of metalloproteinase-3 (TIMP-3) and E-cadherin, concomitant with inhibition of cell migration and invasion. Moreover, knockdown of uPAR potentiated the effects of DADS on MGC-803 cells. These data demonstrate that downregulation of uPAR may partially be responsible for DADS-induced inhibition of ERK/Fra-1 pathway, as well as cell migration and invasion. Thus, the discovery of DADS-induced differential expression proteins is conducive to reveal unknown mechanisms of DADS anti-gastric cancer.
AuthorsBo Su, Jian Su, Hui He, Youhua Wu, Hong Xia, Xi Zeng, Wenxiang Dai, Xiaohong Ai, Hui Ling, Hao Jiang, Qi Su
JournalOncology reports (Oncol Rep) Vol. 33 Issue 5 Pg. 2484-94 (May 2015) ISSN: 1791-2431 [Electronic] Greece
PMID25812569 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Allyl Compounds
  • Cadherins
  • Disulfides
  • Proteome
  • Proto-Oncogene Proteins c-fos
  • Receptors, Urokinase Plasminogen Activator
  • Tissue Inhibitor of Metalloproteinase-3
  • Vimentin
  • fos-related antigen 1
  • diallyl disulfide
  • Cyclin-Dependent Kinases
  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinase 9
Topics
  • Allyl Compounds (pharmacology)
  • Cadherins (metabolism)
  • Cell Line, Tumor
  • Cyclin-Dependent Kinases (metabolism)
  • Disulfides (pharmacology)
  • Down-Regulation (drug effects)
  • Humans
  • MAP Kinase Signaling System (drug effects)
  • Matrix Metalloproteinase 9 (metabolism)
  • Proteome (metabolism)
  • Proteomics (methods)
  • Proto-Oncogene Proteins c-fos (metabolism)
  • Receptors, Urokinase Plasminogen Activator (metabolism)
  • Signal Transduction (drug effects)
  • Stomach Neoplasms (metabolism)
  • Tissue Inhibitor of Metalloproteinase-3 (metabolism)
  • Up-Regulation (drug effects)
  • Urokinase-Type Plasminogen Activator (metabolism)
  • Vimentin (metabolism)

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