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Article

Kaempferol suppresses cell metastasis via inhibition of the ERK-p38-JNK and AP-1 signaling pathways in U-2 OS human osteosarcoma cells

  • Authors:
    • Hui-Jye Chen
    • Chung-Ming Lin
    • Chao-Ying Lee
    • Nai-Chen Shih
    • Shu-Fen Peng
    • Minoru Tsuzuki
    • Sakae Amagaya
    • Wen-Wen Huang
    • Jai-Sing Yang
  • View Affiliations / Copyright

    Affiliations: Graduate Institute of Molecular Systems Biomedicine, China Medical University, Taichung 40402, Taiwan, R.O.C., Department of Biotechnology, Ming Chuan University, Taoyuan 333, Taiwan, R.O.C., School of Pharmacy, China Medical University, Taichung 40402, Taiwan, R.O.C., Department of Pharmacology, China Medical University, Taichung 40402, Taiwan, R.O.C., Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan, R.O.C., Department of Biochemistry, Nihon Pharmaceutical University, Saitama 362-0806, Japan, Department of Kampo Pharmaceutical Sciences, Nihon Pharmaceutical University, Saitama 362-0806, Japan
  • Pages: 925-932
    |
    Published online on: May 23, 2013
       https://doi.org/10.3892/or.2013.2490
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Abstract

Kaempferol is a natural flavonoid that possesses anti-proliferative and apoptosis-inducing activities in several cancer cell lines. In the present study, we investigated the anti-metastatic activity of kaempferol and its molecular mechanism(s) of action in human osteosarcoma cells. Kaempferol displayed inhibitory effects on the invasion and adhesion of U-2 osteosarcoma (OS) cells in a concentration-dependent manner by Matrigel Transwell assay and cell adhesion assay. Kaempferol also inhibited the migration of U-2 OS cells in a concentration-dependent manner at different treatment time points by wound-healing assay. Additional experiments showed that kaempferol treatment reduced the enzymatic activities and protein levels of matrix metalloproteinase (MMP)-2, MMP-9 and urokinase plasminogen activator (uPA) by gelatin and casein-plasminogen zymography assays and western blot analyses. Kaempferol also downregulated the mRNA levels of MMP-2 and MMP-9 by quantitative PCR analyses. Furthermore, kaempferol was able to reduce the protein phosphorylation of ERK, p38 and JNK by western blotting. By electrophoretic mobility-shift assay (EMSA), we demonstrated that kaempferol decreased the DNA binding activity of AP-1, an action likely to result in the reduced expression of MMP-2, MMP-9 and uPA. Collectively, our data showed that kaempferol attenuated the MAPK signaling pathways including ERK, JNK and p38 and resulted in the decreased DNA binding ability of AP-1, and hence, the downregulation in the expression and enzymatic activities of MMP-2, MMP-9 and uPA, contributing to the inhibition of metastasis of U-2 OS cells. Our results suggest a potential role of kaempferol in the therapy of tumor metastasis of OS.
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Spandidos Publications style
Chen H, Lin C, Lee C, Shih N, Peng S, Tsuzuki M, Amagaya S, Huang W and Yang J: Kaempferol suppresses cell metastasis via inhibition of the ERK-p38-JNK and AP-1 signaling pathways in U-2 OS human osteosarcoma cells. Oncol Rep 30: 925-932, 2013.
APA
Chen, H., Lin, C., Lee, C., Shih, N., Peng, S., Tsuzuki, M. ... Yang, J. (2013). Kaempferol suppresses cell metastasis via inhibition of the ERK-p38-JNK and AP-1 signaling pathways in U-2 OS human osteosarcoma cells. Oncology Reports, 30, 925-932. https://doi.org/10.3892/or.2013.2490
MLA
Chen, H., Lin, C., Lee, C., Shih, N., Peng, S., Tsuzuki, M., Amagaya, S., Huang, W., Yang, J."Kaempferol suppresses cell metastasis via inhibition of the ERK-p38-JNK and AP-1 signaling pathways in U-2 OS human osteosarcoma cells". Oncology Reports 30.2 (2013): 925-932.
Chicago
Chen, H., Lin, C., Lee, C., Shih, N., Peng, S., Tsuzuki, M., Amagaya, S., Huang, W., Yang, J."Kaempferol suppresses cell metastasis via inhibition of the ERK-p38-JNK and AP-1 signaling pathways in U-2 OS human osteosarcoma cells". Oncology Reports 30, no. 2 (2013): 925-932. https://doi.org/10.3892/or.2013.2490
Copy and paste a formatted citation
x
Spandidos Publications style
Chen H, Lin C, Lee C, Shih N, Peng S, Tsuzuki M, Amagaya S, Huang W and Yang J: Kaempferol suppresses cell metastasis via inhibition of the ERK-p38-JNK and AP-1 signaling pathways in U-2 OS human osteosarcoma cells. Oncol Rep 30: 925-932, 2013.
APA
Chen, H., Lin, C., Lee, C., Shih, N., Peng, S., Tsuzuki, M. ... Yang, J. (2013). Kaempferol suppresses cell metastasis via inhibition of the ERK-p38-JNK and AP-1 signaling pathways in U-2 OS human osteosarcoma cells. Oncology Reports, 30, 925-932. https://doi.org/10.3892/or.2013.2490
MLA
Chen, H., Lin, C., Lee, C., Shih, N., Peng, S., Tsuzuki, M., Amagaya, S., Huang, W., Yang, J."Kaempferol suppresses cell metastasis via inhibition of the ERK-p38-JNK and AP-1 signaling pathways in U-2 OS human osteosarcoma cells". Oncology Reports 30.2 (2013): 925-932.
Chicago
Chen, H., Lin, C., Lee, C., Shih, N., Peng, S., Tsuzuki, M., Amagaya, S., Huang, W., Yang, J."Kaempferol suppresses cell metastasis via inhibition of the ERK-p38-JNK and AP-1 signaling pathways in U-2 OS human osteosarcoma cells". Oncology Reports 30, no. 2 (2013): 925-932. https://doi.org/10.3892/or.2013.2490
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