Suppression of matrix metalloproteinase-9 by 4-methylumbelliferone.
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.
Nakamura
Rika
R
Department of Medical Technology, Hirosaki University School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan.
Kuwabara
Hiroko
H
Yoneda
Masahiko
M
Yoshihara
Shuichi
S
Ishikawa
Takashi
T
Miura
Tomisato
T
Nozaka
Hiroyuki
H
Nanashima
Naoki
N
Sato
Tatsusuke
T
Nakamura
Toshiya
T
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
D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D006923:Hymecromone; D005780:Gelatin; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase