title: Suppression of matrix metalloproteinase-9 by 4-methylumbelliferone.
abstract: OHK cells, a human lymphoma cell line, are known to produce large amounts of hyaluronan. We investigated the effect of 4-methylumbelliferone, an inhibitor of hyaluronan synthesis, on the activity of matrix metalloproteinases in OHK cells. Matrix metalloproteinase-9 was detected on gelatin zymography as the main metalloproteinase excreted into the medium of cultured OHK cells, and 4-methylumbelliferone added to the medium decreased the activity of the enzyme in a dose-dependent manner. Addition of Streptomyces hyaluronidase to the medium during cultivation did not decrease the enzyme activity. Reverse transcription-polymerase chain reaction revealed that 4-methylumbelliferone markedly decreased the level of mRNA for matrix metalloproteinase-9 in cultured OHK cells. A similar decrease of the activity of matrix metalloproteinase-9 by 4-methylumbelliferone was also observed in cultured human breast and colon carcinoma cells. These results suggest that 4-methylumbelliferone suppresses the expression of matrix metalloproteinase-9 in cultured cancer cells.
authors.affiliation: Department of Medical Technology, Hirosaki University School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Nakamura
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kuwabara
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yoneda
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yoshihara
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Tomisato
authors.initials: T
authors.lastname: Miura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nozaka
authors.forename: Naoki
authors.initials: N
authors.lastname: Nanashima
authors.forename: Tatsusuke
authors.initials: T
authors.lastname: Sato
authors.forename: Toshiya
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D045744:Cell Line, Tumor; D005780:Gelatin / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D006923:Hymecromone / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D006923:Hymecromone; D005780:Gelatin; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase