EFFECTS OF HYALURONAN SYNTHASE INHIBITORS, 4-METHYLUMBELLIFERONEAND 4-METHYLESCULETIN ON HUMAN PLEURAL MALIGNANT MESOTHELIOMA CELLS (NCI-H2052)

Hyaluronan (HA) is a major component of the pericellular matrix, and is implicated in cell adhesion, invasion. and tumor metastasis. We have reported that 4-methylumbelliferone (MU) inhibits HA synthesis by cultured skin fibroblasts, melanoma cells, and pancreatic cancer cells. We focused in the present study, on mesothelioma which has an extremely poor prognosis, and in which no effective therapy has yet been established. We investigated dealing with this neoplasm whether MU and 4-methylesculetin (ME), a MU derivative, are able to inhibit HA synthesis by the mesothelioma cell line NCI-H2052. MU inhibited HA synthesis by about 20%, and ME by about 40%, in comparison with the control group. MU inhibited the adhesion of NCI-H2052 cells by about 30%, and ME by about 50%, compared with the untreated control. MU inhibited cell locomotion by about 30%. and ME by about 40%. It is suggested through these results suggest that MU and ME inhibit HA synthesis. adhesion, and locomotion by human mesothelioma cells and weaken their pericellular matrix, and that the inhibitory effect of ME on HA synthesis is stronger than that of MU. It is presumed that both MU and ME may have potential as new therapeutic or prophylactic medicines against mesothelioma. Hirosaki Med. J, 59: 118-127, 2008 ~ ~ ~Y~O~mft~~~M~~~4 -~~~~~~~7~O~~~U4 -~ ~~~~~~7~O~a_W~~~ 4-~~~~~~~~~~~_mt t~ JjtJJl~:~'!T ~ ~ y JvO ~mft~m~~)Jm~~~'! ~ fi ~ ~ ~ ~ ~