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.

PMID: 20204301 [PubMed − in process] Source: National Library of Medicine.