title: Fisetin suppresses ADAM9 expression and inhibits invasion of glioma cancer cells through increased phosphorylation of ERK1/2.
abstract: Fisetin (3,3',4',7-tetrahydroxyflavone) is a naturally occurring flavonoid which is widely distributed in plants. It has been reported to possess some anticancer and anti-invasive capabilities. We set out to explore the effects of fisetin on antimetastatic and its mechanism of action in GBM8401 cells. The results indicated that fisetin exhibited effective inhibition of cell migration and inhibited the invasion of GBM8401 cells under non-cytotoxic concentrations. To identify the potential targets of fisetin, human proteinase antibody array analysis was performed, and the results indicated that the fisetin treatment inhibited the expression of ADAM9 protein and mRNA, which are known to contribute to the progression of glioma cancer. Our results showed that fisetin phosphorylated ERK1/2 in a sustained way that contributed to the inhibited ADAM9 protein and mRNA expression determined by Western blot and RT-PCR. Moreover, inhibition of ERK1/2 by U0126 or transfection with the siERK plasmid significantly abolished the fisetin-inhibited migration and invasion through activation of the ERK1/2 pathway. In summary, our results suggest that fisetin might be a potential therapeutic agent against human glioma cells based on its capacity to activate ERK1/2 and to inhibit ADAM9 expression.
authors.affiliation: Division of Neurosurgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Chien-Min
authors.initials: CM
authors.lastname: Chen
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Hsieh
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Hwang
authors.forename: Hsun-Jin
authors.initials: HJ
authors.lastname: Jan
authors.forename: Shu-Ching
authors.initials: SC
authors.lastname: Hsieh
authors.forename: Shin-Huey
authors.initials: SH
authors.lastname: Lin
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Lai
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology
chemical_list: D005419:Flavonoids; D044948:Flavonols; D008565:Membrane Proteins; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D051722:ADAM Proteins; C098339:ADAM9 protein, human; C017875:fisetin