Suppression of matrix metalloproteinase-9 by 4-methylumbelliferone

• Published in: Cell biology international 2007-09, Vol.31 (9), p.1022-1026
• Main Authors: Nakamura, Rika, Kuwabara, Hiroko, Yoneda, Masahiko, Yoshihara, Shuichi, Ishikawa, Takashi, Miura, Tomisato, Nozaka, Hiroyuki, Nanashima, Naoki, Sato, Tatsusuke, Nakamura, Toshiya
• Format: Article
• Language: English
• Subjects: 4-Methylumbelliferone; Cell Line, Tumor; Gelatin - metabolism; Gene Expression Regulation, Enzymologic - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Humans; Hyaluronan; Hyaluronic Acid - biosynthesis; Hyaluronoglucosaminidase - metabolism; Hymecromone - pharmacology; Matrix Metalloproteinase Inhibitors; Matrix metalloproteinase-9; OHK cells; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1016/j.cellbi.2007.03.016

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.