p38 MAPK plays a distinct role in sulforaphane-induced up-regulation of ARE-dependent enzymes and down-regulation of COX-2 in human bladder cancer cells

  • Authors:
    • Yujuan Shan
    • Xiaoxue Wang
    • Wei Wang
    • Canxia He
    • Yongping Bao
  • View Affiliations

  • Published online on: April 1, 2010     https://doi.org/10.3892/or_00000742
  • Pages: 1133-1138
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Abstract

Sulforaphane, a well-characterised dietary isothiocyanate, has been demonstrated to be a potent anti-carcinogenic agent in numerous cancer models, including in bladder cancer cells. In the present study, sulforaphane up-regulated the expression of two Nrf2-dependent enzymes, glutathione transferase (GSTA1-1) and thioredoxin reductase (TR-1), and down-regulated cyclooxygenase 2 (COX-2) in human bladder cancer T24 cells. This action of sulforaphane was associated with the p38 MAPK activity. When a specific p38 MAPK inhibitor, SB202190, was used, both sulforaphane-induced up-regulation of GSTA1-1 and TR-1 and down-regulation of COX-2 were eliminated; in contrast, an activator of p38 MAPK, anisomycin, enhanced the effect of sulforaphane on modulation of GST, TR-1 and COX-2 expression. Moreover, it was established that anisomycin increased nuclear translocation of Nrf2, whereas SB202190 abrogated sulforaphane-induced Nrf2 translocation into the nucleus. In summary, these data suggest that p38 MAPK activation can regulate Nrf2-antioxidant response element (ARE)-driven enzymes and COX-2 expression, thereby facilitating the role of sulforaphane in cancer prevention. This study strongly supports the contention that p38 MAPK is a pivotal and efficient target of sulforaphane in the chemoprevention of bladder cancer.

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April 2010
Volume 23 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Shan Y, Wang X, Wang W, He C and Bao Y: p38 MAPK plays a distinct role in sulforaphane-induced up-regulation of ARE-dependent enzymes and down-regulation of COX-2 in human bladder cancer cells. Oncol Rep 23: 1133-1138, 2010
APA
Shan, Y., Wang, X., Wang, W., He, C., & Bao, Y. (2010). p38 MAPK plays a distinct role in sulforaphane-induced up-regulation of ARE-dependent enzymes and down-regulation of COX-2 in human bladder cancer cells. Oncology Reports, 23, 1133-1138. https://doi.org/10.3892/or_00000742
MLA
Shan, Y., Wang, X., Wang, W., He, C., Bao, Y."p38 MAPK plays a distinct role in sulforaphane-induced up-regulation of ARE-dependent enzymes and down-regulation of COX-2 in human bladder cancer cells". Oncology Reports 23.4 (2010): 1133-1138.
Chicago
Shan, Y., Wang, X., Wang, W., He, C., Bao, Y."p38 MAPK plays a distinct role in sulforaphane-induced up-regulation of ARE-dependent enzymes and down-regulation of COX-2 in human bladder cancer cells". Oncology Reports 23, no. 4 (2010): 1133-1138. https://doi.org/10.3892/or_00000742