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Depression: 21st Century Solutions + The Dark Side of Wheat

Abstract Title:

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

Abstract Source:

Int J Oncol. 2009 Apr;34(4):1129-34. PMID: 19287971

Abstract Author(s):

Yujuan Shan, Kun Wu, Wei Wang, Shuran Wang, Na Lin, Ruifang Zhao, Aedin Cassidy, Yongping Bao

Article Affiliation:

School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK.

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 microM) induced nuclear translocation of NF-kappaB 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-kappaB translocation to the nucleus, promoted NF-kappaB 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.

Study Type : In Vitro Study

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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