4-Hydroxybutenolide impairs cell migration, and invasion of human oral cancer SCC-4 cells via the inhibition of NF-κB and MAPK signaling pathways

  • Authors:
    • Fu-Shun Yu
    • Meng-Liang Lin
    • Shu-Chun Hsu
    • Chien-Chih Yu
    • Yi-Ping Huang
    • Yueh-Hsiung Kuo
    • Jing-Gung Chung
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  • Published online on: May 24, 2016     https://doi.org/10.3892/ijo.2016.3537
  • Pages: 579-588
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Abstract

4-Hydroxybutenolide (K87), a synthetic compound from furfuryl alcohol via photooxidation, was used to investigate whether it can inhibit mobility, migration and invasion of SCC-4 human oral cancer cells in vitro. Cell viability was measured by flow cytometric assay, the enzymatic activities of MMP-2/9 were assayed by gelatin zymography analysis, the protein levels were assayed by western blotting, confocal laser microscopy and EMSA assay, and the gene expression of MMP-2/-7, FAK and ROCK1 mRNA were assayed by PCR. K87 decreased the percentage of viable cells in dose-dependent manner. K87 suppressed cell mobility, migration and invasion of SCC-4 cells dose-dependently. K87 inhibited the enzymatic activities of MMP-2/9 of SCC-4 cells. Western blot analysis revealed that K87 decreased the protein levels in NF-κBp65, COX-2, ROCK1 and Rho A, MMP-1, -2,- 7, -9, VEGF, GRB2, SOS1, PI3K, PKC, PERK, p-PERK, FAK, MEKK3, MKK7, ERK1/2, JNK1/2, p-p38, p38, p-c-Jun, AKT, TIMP2, but increased the protein levels of iNOS, Ras, IRE-1α, p-c-JNK, p-AKT(308), p-AKT(473) and TIMP1. Results from PCR indicated that K87 inhibited the gene expression of MMP-2/-7, FAK and ROCK1 mRNA. Furthermore, confocal laser microscopy was used to confirm that K87 inhibited the translocation of RHOA and ROCK1 in SCC-4 cells. EMSA assay also show that K87 suppressed the nuclear activation of NF-κB and these effects are time-dependent. Western blotting assay indicated that expression of NF-κBp105, NF-κBp50 and NF-κBp65 proteins were decreased and these effects are time-dependent. Based on these observations, we suggest that K87 may be used as a potential agent for anticancer metastasis of human oral cancer in the future.
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August-2016
Volume 49 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yu F, Lin M, Hsu S, Yu C, Huang Y, Kuo Y and Chung J: 4-Hydroxybutenolide impairs cell migration, and invasion of human oral cancer SCC-4 cells via the inhibition of NF-κB and MAPK signaling pathways. Int J Oncol 49: 579-588, 2016.
APA
Yu, F., Lin, M., Hsu, S., Yu, C., Huang, Y., Kuo, Y., & Chung, J. (2016). 4-Hydroxybutenolide impairs cell migration, and invasion of human oral cancer SCC-4 cells via the inhibition of NF-κB and MAPK signaling pathways. International Journal of Oncology, 49, 579-588. https://doi.org/10.3892/ijo.2016.3537
MLA
Yu, F., Lin, M., Hsu, S., Yu, C., Huang, Y., Kuo, Y., Chung, J."4-Hydroxybutenolide impairs cell migration, and invasion of human oral cancer SCC-4 cells via the inhibition of NF-κB and MAPK signaling pathways". International Journal of Oncology 49.2 (2016): 579-588.
Chicago
Yu, F., Lin, M., Hsu, S., Yu, C., Huang, Y., Kuo, Y., Chung, J."4-Hydroxybutenolide impairs cell migration, and invasion of human oral cancer SCC-4 cells via the inhibition of NF-κB and MAPK signaling pathways". International Journal of Oncology 49, no. 2 (2016): 579-588. https://doi.org/10.3892/ijo.2016.3537