title: Study of hyaluronan synthase inhibitor, 4-methylumbelliferone derivatives on human pancreatic cancer cell (KP1-NL).
abstract: The structure of 4-methylumbelliferone (MU) consists of coumarin with 4-methyl group and 7-hydroxy group. MU inhibits HA synthesis and pericellular HA matrix formation. In this study, we used 10 MU derivatives which have hydroxy groups and methyl groups at various positions of coumarin to investigate a more effective HA inhibitor than MU. First, human pancreatic cancer cell (KP1-NL) growth assay was analyzed by Alamar Blue to determine the non-toxic concentration of MU derivatives, and the inhibitory effect on HA synthesis in the cell cultures was analyzed by HA measuring kit. Next, cell surfaces of cancer cells were analyzed by particle-exclusion assay. In conclusion, both hydroxy and methyl groups are necessary for HA inhibition by MU, and two hydroxy groups inhibited HA synthesis more strongly than MU.
authors.affiliation: Department of Biochemistry, Hirosaki University School of Medicine, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Morohashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kon
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakai
authors.forename: Masanori
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kakizaki
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yoshihara
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Sasaki
authors.forename: Keiichi
authors.initials: K
authors.lastname: Takagaki
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000096:biosynthesis; D006923:Hymecromone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D006923:Hymecromone; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases