Inhibition of urinary bladder carcinogenesis by broccoli sprouts

B149

Isothiocyanates (ITCs) are a well-known class of cancer chemopreventive agents, and broccoli sprouts are a rich source of several ITCs. We report herein that dietary administration to rats of a freeze-dried aqueous extract of broccoli sprouts significantly and dose-dependently inhibited bladder cancer development induced by N-butyl-N-(4-hydroxybutyl) nitrosamine. The incidence, multiplicity, size and progression of bladder cancer were all inhibited by the extract, while the extract itself caused no histological changes in the bladder. Moreover, inhibition of bladder carcinogenesis by the extract was associated with significant induction of glutathione S-transferase and NAD(P)H:quinone oxidoreductase 1 in the bladder, enzymes that are known to be important protectants against oxidants and carcinogens. ITCs are metabolized to dithiocarbamates (DTCs) in vivo, but DTCs readily dissociate to ITCs. We found that more than 70% of the ITCs present in the extract were excreted in the urine as ITC equivalents (ITCs + DTCs) in 12 h after a single oral dose, indicating high bioavailability and rapid urinary excretion. In addition, the concentrations of ITC equivalents in the urine of extract-treated rats were 2-3 orders of magnitude higher than those in plasma, indicating that the bladder epithelium, the major site of bladder cancer development, is most exposed to orally dosed ITC. Indeed, tissue levels of ITC equivalents in the bladder were significantly higher than in the liver. In conclusion, broccoli sprout extract is a highly promising substance for bladder cancer prevention and the ITCs in the extract are selectively delivered to the bladder epithelium through urinary excretion.