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Sulforaphane (SFN) is one of the bioactive components of cruciferous vegetables and highly protective against different types of cancer models. Its effect on bladder cancer prevention has not been studied. We investigated the chemopreventive activity of SFN against bladder cancer and found that SFN had very potent growth inhibitory effects on both highly metastatic (253J B-V) and low metastatic (RT-4) bladder cancer cells in vitro. The mechanisms behind its activity were by G2/M arrest and by induction of apoptosis. To investigate detailed mechanisms of the growth inhibitory activity of SFN we performed Affymetrix microarray assays to determine its effect on modulation of different types of genes specifically related to cell cycle, apoptosis and proliferation. We observed several candidate genes whose activities in bladder cancer cells were not previously reported. We also identified new genes that are related to modulation of cell proliferation, cell cycle progression and apoptosis by SFN. The gene expression was verified by real time RT-PCR. We also applied an orthotopic bladder tumor animal model to determine the effect of SFN on the growth and metastasis of 253J B-V bladder cancer cells. To our surprising, SFN treatment showed growth stimulatory effect on 253J B-V tumors in vivo. Mice treated with SFN at 1mg/kg BW dramatically increased tumor growth rate and reduced survival rate. The results derived from our studies suggest that certain SFN metabolite(s) may have growth stimulatory effect on bladder tumors in the orthotopic bladder tumor model. Our results reinforce the importance to use orthotopic bladder tumor animal model for bladder cancer prevention and treatment studies.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]