Study of hyaluronan synthase inhibitor, 4-methylumbelliferone derivatives on human pancreatic cancer cell (KP1-NL).
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.
Morohashi
Hajime
H
Department of Biochemistry, Hirosaki University School of Medicine, Japan.
Kon
Atsushi
A
Nakai
Makoto
M
Yamaguchi
Masanori
M
Kakizaki
Ikuko
I
Yoshihara
Shuichi
S
Sasaki
Mutsuo
M
Takagaki
Keiichi
K
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
D004791:Enzyme Inhibitors; D006923:Hymecromone; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases