Antitumor effects of the novel quinazolinone MJ-33: Inhibition of metastasis through the MAPK, AKT, NF-κB and AP-1 signaling pathways in DU145 human prostate cancer cells

  • Authors:
    • Mann-Jen Hour
    • Shih-Chang Tsai
    • Hsi-Chin Wu
    • Meng-Wei Lin
    • Jing‑Gung  Chung
    • Jin-Bin Wu
    • Jo-Hua Chiang
    • Minoru Tsuzuki
    • Jai-Sing Yang
  • View Affiliations

  • Published online on: July 18, 2012     https://doi.org/10.3892/ijo.2012.1560
  • Pages: 1513-1519
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Quinazolinone compounds have been shown to have antitumor activity in many human cancer cell lines. In the present study, we investigated the anti-metastatic activity of MJ-33 (2-(3-ethoxyphenyl)-6-pyrrolidinylquinazolinone), a novel quinazolinone derivate, and the signaling pathway of MJ-33 in human prostate cells. MJ-33 exhibited a growth inhibitory effect on DU145, LNCaP and PC-3 cells by MTT assay. DU145 cells showed greater sensitivity to the growth inhibition of MJ-33 than that of LNCaP and PC-3 cells. MJ-33 also had an inhibitory effect on the invasion, migration and adhesion of DU145 cells using Boyden chamber transwell assays, wound-healing and adhesion assay. In addition, MJ-33 inhibited cell metastasis through the reduction of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and urokinase-type plasminogen activator (u-PA) enzyme activities and protein levels by gelatin zymography assay and western blot analysis, respectively. MJ-33 reduced the protein levels of p-JNK, p-p38, p-ERK, p-AKT and nuclear NF-κB (p65), c-fos and c-Jun protein levels by western blotting. Using electrophoretic mobility-shift assay (EMSA), we demonstrated that MJ-33 blocked the activation of transcription factor AP-1 (activator protein-1) and NF-κB, which led to the inhibition of MMP-2 and MMP-9 expression. Collectively, our data showed that MJ-33 decreased protein levels of MAPKs (mitogen-activated protein kinases), AKT, AP-1 and NF-κB, resulting in the inhibition of matrix metalloproteinases. Downregulation of MMP-2 and MMP-9 reduces the invasion, migration and adhesion activities of DU145 cells. MJ-33 may be a promising agent against prostate cancer metastasis.
View Figures
View References

Related Articles

Journal Cover

October 2012
Volume 41 Issue 4

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Hour M, Tsai S, Wu H, Lin M, Chung JG, Wu J, Chiang J, Tsuzuki M and Yang J: Antitumor effects of the novel quinazolinone MJ-33: Inhibition of metastasis through the MAPK, AKT, NF-κB and AP-1 signaling pathways in DU145 human prostate cancer cells. Int J Oncol 41: 1513-1519, 2012
APA
Hour, M., Tsai, S., Wu, H., Lin, M., Chung, J., Wu, J. ... Yang, J. (2012). Antitumor effects of the novel quinazolinone MJ-33: Inhibition of metastasis through the MAPK, AKT, NF-κB and AP-1 signaling pathways in DU145 human prostate cancer cells. International Journal of Oncology, 41, 1513-1519. https://doi.org/10.3892/ijo.2012.1560
MLA
Hour, M., Tsai, S., Wu, H., Lin, M., Chung, J., Wu, J., Chiang, J., Tsuzuki, M., Yang, J."Antitumor effects of the novel quinazolinone MJ-33: Inhibition of metastasis through the MAPK, AKT, NF-κB and AP-1 signaling pathways in DU145 human prostate cancer cells". International Journal of Oncology 41.4 (2012): 1513-1519.
Chicago
Hour, M., Tsai, S., Wu, H., Lin, M., Chung, J., Wu, J., Chiang, J., Tsuzuki, M., Yang, J."Antitumor effects of the novel quinazolinone MJ-33: Inhibition of metastasis through the MAPK, AKT, NF-κB and AP-1 signaling pathways in DU145 human prostate cancer cells". International Journal of Oncology 41, no. 4 (2012): 1513-1519. https://doi.org/10.3892/ijo.2012.1560