title: Diallyl disulfide suppresses epithelial-mesenchymal transition, invasion and proliferation by downregulation of LIMK1 in gastric cancer.
abstract: Diallyl disulfide (DADS) has been shown to have multi-targeted antitumor activities. We have previously discovered that it has a repressive effect on LIM kinase-1 (LIMK1) expression in gastric cancer MGC803 cells. This suggests that DADS may inhibit epithelial-mesenchymal transition (EMT) by downregulating LIMK1, resulting in the inhibition of invasion and growth in gastric cancer. In this study, we reveal that LIMK1 expression is correlated with tumor differentiation, invasion depth, clinical stage, lymph node metastasis, and poor prognosis. DADS downregulated the Rac1-Pak1/Rock1-LIMK1 pathway in MGC803 cells, as shown by decreased p-LIMK1 and p-cofilin1 levels, and suppressed cell migration and invasion. Knockdown and overexpression experiments performed in vitro demonstrated that downregulating LIMK1 with DADS resulted in restrained EMT that was coupled with decreased matrix metalloproteinase-9 (MMP-9) and increased tissue inhibitor of metalloproteinase-3 (TIMP-3) expression. In in vitro and in vivo experiments, the DADS-induced suppression of cell proliferation was enhanced and antagonized by the knockdown and overexpression of LIMK1, respectively. Similar results were observed for DADS-induced changes in the expression of vimentin, CD34, Ki-67, and E-cadherin in xenografted tumors. These results indicate that downregulation of LIMK1 by DADS could explain the inhibition of EMT, invasion and proliferation in gastric cancer cells.
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, China.|Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, 421001 Hunan, China.|Key Laboratory for Pharmacoproteomics of Hunan Provincial University, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, 421001 Hunan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Su
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, China.|Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, 421001 Hunan, China.|Department of Pathology, Second Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Su
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, China.|Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, 421001 Hunan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, China.|Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, 421001 Hunan, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, China.|Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, 421001 Hunan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xia
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, China.|Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, 421001 Hunan, China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Ma
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, China.|Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, 421001 Hunan, China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Zhou
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, China.|Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, 421001 Hunan, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, China.|Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, 421001 Hunan, China.
authors.forename: Bang-Min
authors.initials: BM
authors.lastname: Yang
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, China.
authors.forename: You-Hua
authors.initials: YH
authors.lastname: Wu
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, China.|Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, 421001 Hunan, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Ai
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, China.|Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, 421001 Hunan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ling
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, 421001 Hunan, China.|Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, 421001 Hunan, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Su
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D051338:Cofilin 1 / Q000378:metabolism; D004220:Disulfides / Q000494:pharmacology*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D054461:Lim Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000401:mortality / Q000473:pathology*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism; D014183:Transplantation, Heterologous; D014746:Vimentin / Q000378:metabolism; D054462:p21-Activated Kinases / Q000096:biosynthesis; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis; D054460:rho-Associated Kinases / Q000096:biosynthesis
chemical_list: D000498:Allyl Compounds; D018952:Antigens, CD34; C495810:CFL1 protein, human; D015820:Cadherins; D051338:Cofilin 1; D004220:Disulfides; D019394:Ki-67 Antigen; C107953:RAC1 protein, human; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D014746:Vimentin; C028009:diallyl disulfide; C515892:LIMK1 protein, human; D054461:Lim Kinases; C515903:PAK1 protein, human; C515851:ROCK1 protein, human; D054462:p21-Activated Kinases; D054460:rho-Associated Kinases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D020830:rac1 GTP-Binding Protein
keywords: LIMK1; diallyl disulfide; gastric cancer cell epithelial-mesenchymal transition; invasion; proliferation