Tumor Biology

, Volume 36, Issue 5, pp 3407–3415 | Cite as

Fisetin suppresses ADAM9 expression and inhibits invasion of glioma cancer cells through increased phosphorylation of ERK1/2

  • Chien-Min Chen
  • Yi-Hsien Hsieh
  • Jin-Ming Hwang
  • Hsun-Jin Jan
  • Shu-Ching Hsieh
  • Shin-Huey Lin
  • Chung-Yu Lai
Research Article


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.


Glioma cancer cells Fisetin Migration Invasion ADAM9 



This work was supported by grants from Chung Shan Medical University (CSMU-INT-102-15) and Chung Shan Medical University and Changhua Christian Hospital, Changhua, Taiwan (CSMU-CCH-103-02).

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Chien-Min Chen
    • 1
  • Yi-Hsien Hsieh
    • 2
  • Jin-Ming Hwang
    • 3
  • Hsun-Jin Jan
    • 4
  • Shu-Ching Hsieh
    • 5
  • Shin-Huey Lin
    • 6
  • Chung-Yu Lai
    • 7
  1. 1.Division of Neurosurgery, Department of SurgeryChanghua Christian HospitalChanghuaTaiwan
  2. 2.Department of Biochemistry, School of MedicineChung Shan Medical UniversityTaichungTaiwan
  3. 3.Department of Applied Chemistry, School of Medicine, College of MedicineChung Shan Medical UniversityTaichungTaiwan
  4. 4.Graduate Institute of Pharmaceutical Science and TechnologyCentral Taiwan University of Science and TechnologyTaichungTaiwan
  5. 5.Institute of MedicineChung Shan Medical UniversityTaichungTaiwan
  6. 6.Institute of Biochemistry and Biotechnology, College of MedicineChung Shan Medical UniversityTaichungTaiwan
  7. 7.Department of Surgery, Chung-Kang BranchCheng-Ching General HospitalTaichungTaiwan

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