Inhibition of urinary bladder carcinogenesis by broccoli sprouts.
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.
Munday
Rex
R
AgResearch Limited, Ruakura Agricultural Research Center, Hamilton, New Zealand.
Mhawech-Fauceglia
Paulette
P
Munday
Christine M
CM
Paonessa
Joseph D
JD
Tang
Li
L
Munday
John S
JS
Lister
Carolyn
C
Wilson
Paula
P
Fahey
Jed W
JW
Davis
Warren
W
Zhang
Yuesheng
Y
D000821:Animal Feed; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001937:Brassica; D002085:Butylhydroxybutylnitrosamine / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D008954:Models, Biological; D011808:Quinone Reductases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000517:prevention & control*
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; C037152:isothiocyanic acid; D002085:Butylhydroxybutylnitrosamine; C041831:NADH dehydrogenase (quinone); D011808:Quinone Reductases; D005982:Glutathione Transferase