Isothiocyanates are a well-known class of
cancer chemopreventive agents, and broccoli sprouts are a rich source of several
isothiocyanates. 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 histologic 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 important protectants against
oxidants and
carcinogens.
Isothiocyanates are metabolized to dithiocarbamates in vivo, but dithiocarbamates readily dissociate to
isothiocyanates. We found that >70% of the
isothiocyanates present in the extract were excreted in the urine as
isothiocyanate equivalents (
isothiocyanates + dithiocarbamates) in 12 h after a single p.o. dose, indicating high bioavailability and rapid urinary excretion. In addition, the concentrations of
isothiocyanate equivalents in the urine of extract-treated rats were 2 to 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 p.o. dosed
isothiocyanate. Indeed, tissue levels of
isothiocyanate 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
isothiocyanates in the extract are selectively delivered to the bladder epithelium through urinary excretion.