Dietary Isothiocyanates Inhibit the Growth of Human Bladder Carcinoma Cells -- Tang and Zhang 134 (8): 2004 -- Journal of Nutrition 


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© 2004 The American Society for Nutritional Sciences J. Nutr. 134:2004-2010, 
August 2004




Nutrition and Cancer
Dietary Isothiocyanates Inhibit the Growth of Human Bladder Carcinoma Cells1 
Li Tang and Yuesheng Zhang2 
Department of Chemoprevention, Roswell Park Cancer Institute, Buffalo, NY 14263 
2To whom correspondence should be addressed. E-mail: 
yuesheng.zhang@roswellpark.org.
Many isothiocyanates (ITCs), some of which are abundant in cruciferous 
vegetables, have been repeatedly shown to inhibit carcinogenesis in a variety of 
rodent organs. However, several naturally occurring ITCs also promoted bladder 
tumorigenesis in rodents, raising the question of whether ITCs behave 
differently in bladder cells. Alternatively, the observed carcinogenic effects 
of ITCs may result from prolonged exposure of the bladder epithelium, where the 
tumors originate, to high concentrations of electrophilic ITCs in the urine. 
Ingested ITCs are almost exclusively excreted and highly concentrated in the 
urine as N-acetylcysteine conjugates (NAC-ITC). While several NAC-ITCs also are 
known anticarcinogens, they are unstable and readily dissociate into parent 
ITCs. In this study, ITCs, including those that have carcinogenic potential in 
the rodent bladders, induced apoptosis and/or arrested cell-cycle progression in 
2 human bladder carcinoma lines (UM-UC-3 and T24) at 7.5–30 µmol/L. Multiple 
caspases, including caspase-9, -8, and -3, as well as 
poly(ADP-ribose)polymerase, were cleaved upon ITC exposure. The ITCs blocked 
cell-cycle progression at the G2/M and/or S phases in these cells and 
downregulated several cell-cycle regulators. However, further increases in ITC 
concentrations abolished their activities, described above. These findings show 
that urinary ITC concentrations may need to be maintained at low micromolar 
concentrations for bladder cancer prevention. 



KEY WORDS: • isothiocyanate • bladder cancer • chemoprevention • chemopreventive 
mechanisms of isothiocyanates








       
Copyright © 2004 by American Society for Nutrition