title: Inhibition of matrix metalloproteinase activities and tightening of tight junctions by diallyl disulfide in AGS human gastric carcinoma cells.
abstract: The effect of diallyl disulfide (DADS), a major component of an oil-soluble allyl sulfide garlic (Allium sativum) derivative, on the correlation between anti-invasive activity and tightening of tight junctions (TJs) was investigated in human gastric adenocarcinoma AGS cells. Our data indicated that the inhibitory effects of DADS on cell motility and invasiveness were found to be associated with increased tightness of the TJs, which was demonstrated by an increase in transepithelial electrical resistance. Activities of matrix metalloprotease (MMP)-2 and -9 in AGS cells were dose-dependently inhibited by treatment with DADS, and this was also correlated with a decrease in expression of their mRNA and proteins; however, tissue inhibitor of metalloproteinase (TIMP)-1 and -2 mRNA levels and proteins were increased. Additionally, immunoblotting results indicated that DADS repressed the levels of claudin proteins (claudin-2, -3, and -4), major components of TJs that play key roles in control and selectivity of paracellular transport. Although further studies are needed, these results suggest that DADS treatment may inhibit tumor cell motility and invasion and, therefore, act as a dietary source to decrease the risk of cancer metastasis.
authors.affiliation: Dept. of Pharmacy, Pusan Natl. Univ., Busan 609-735, Republic of Korea.
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Park
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Hwang
authors.forename: Young-Whan
authors.initials: YW
authors.lastname: Choi
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004220:Disulfides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005737:Garlic / Q000737:chemistry*; D005786:Gene Expression Regulation; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D013274:Stomach Neoplasms / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D000498:Allyl Compounds; C491875:CLDN2 protein, human; C568122:CLDN3 protein, human; C568157:CLDN4 protein, human; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; D004220:Disulfides; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D012333:RNA, Messenger; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C028009:diallyl disulfide; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9