Sulforaphane down-regulates COX-2 expression by activating p38 and inhibiting NF-κB-DNA-binding activity in human bladder T24 cells

  • Authors:
    • Yujuan Shan
    • Kun Wu
    • Wei Wang
    • Shuran Wang
    • Na Lin
    • Ruifang Zhao
    • Aedin Cassidy
    • Yongping Bao
  • View Affiliations

  • Published online on: April 1, 2009     https://doi.org/10.3892/ijo_00000240
  • Pages: 1129-1134
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Abstract

Cyclooxygenase-2 (COX-2) overexpression has been associated with the grade, prognosis and recurrence of transitional cell carcinoma (TCC) of the bladder. In this study, sulforaphane, a dietary isothiocyanate, down-regulated COX-2 expression in human bladder transitional cancer T24 cells at both transcriptional- and translational levels. Sulforaphane (5-20 µM) induced nuclear translocation of NF-κB and reduced its binding to the COX-2 promoter, a key mechanism for suppressing COX-2 expression by sulforaphane. Moreover, sulforaphane increased expression of p38 and phosphorylated-p38 protein. A specific inhibitor of p38 MAPK, SB202190, was used to further investigate its pivotal role in sulforaphane-mediated down-regulation of COX-2. Exposure of T24 cells to SB202190 1 hour prior to sulforaphane treatment abolished the effect of sulforaphane on COX-2 mRNA down-regulation, but enhanced COX-2 transcription. Furthermore, SB202190 alone induced NF-κB translocation to the nucleus, promoted NF-κB binding to the COX-2 promoter and resulted in up-regulation of COX-2 expression. Taken together, these data suggest that p38 is essential in sulforaphane-mediated COX-2 suppression and provide new insights into the molecular mechanisms of sulforaphane in the chemoprevention of bladder cancer.

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April 2009
Volume 34 Issue 4

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

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APA
Shan, Y., Wu, K., Wang, W., Wang, S., Lin, N., Zhao, R. ... Bao, Y. (2009). Sulforaphane down-regulates COX-2 expression by activating p38 and inhibiting NF-κB-DNA-binding activity in human bladder T24 cells. International Journal of Oncology, 34, 1129-1134. https://doi.org/10.3892/ijo_00000240
MLA
Shan, Y., Wu, K., Wang, W., Wang, S., Lin, N., Zhao, R., Cassidy, A., Bao, Y."Sulforaphane down-regulates COX-2 expression by activating p38 and inhibiting NF-κB-DNA-binding activity in human bladder T24 cells". International Journal of Oncology 34.4 (2009): 1129-1134.
Chicago
Shan, Y., Wu, K., Wang, W., Wang, S., Lin, N., Zhao, R., Cassidy, A., Bao, Y."Sulforaphane down-regulates COX-2 expression by activating p38 and inhibiting NF-κB-DNA-binding activity in human bladder T24 cells". International Journal of Oncology 34, no. 4 (2009): 1129-1134. https://doi.org/10.3892/ijo_00000240