title: 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.
authors: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Bo
authors: B
authors: Su
authors: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Jian
authors: J
authors: Su
authors: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Hui
authors: H
authors: He
authors: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Youhua
authors: Y
authors: Wu
authors: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Hong
authors: H
authors: Xia
authors: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Xi
authors: X
authors: Zeng
authors: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Wenxiang
authors: W
authors: Dai
authors: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Xiaohong
authors: X
authors: Ai
authors: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Hui
authors: H
authors: Ling
authors: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Hao
authors: H
authors: Jiang
authors: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Qi
authors: Q
authors: Su
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004220:Disulfides / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000378:metabolism*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D000099169:Fos-Related Antigen 1
chemical_list: D000498:Allyl Compounds; D015820:Cadherins; D018844:Cyclin-Dependent Kinases; D004220:Disulfides; D020780:Matrix Metalloproteinase 9; D020543:Proteome; D016760:Proto-Oncogene Proteins c-fos; D055293:Receptors, Urokinase Plasminogen Activator; D019717:Tissue Inhibitor of Metalloproteinase-3; D014568:Urokinase-Type Plasminogen Activator; D014746:Vimentin; D000099169:Fos-Related Antigen 1; C028009:diallyl disulfide