QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tang, L. Articles by Zhang, Y. Search for Related Content PubMed PubMed Citation Articles by Tang, L. Articles by Zhang, Y.

---

Nutrition and Cancer

Dietary Isothiocyanates Inhibit the Growth of Human Bladder Carcinoma Cells¹

Department of Chemoprevention, Roswell Park Cancer Institute, Buffalo, NY 14263

²To whom correspondence should be addressed. E-mail: yuesheng.zhang{at}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

This article has been cited by other articles:

				L. Tang, G. R. Zirpoli, K. Guru, K. B. Moysich, Y. Zhang, C. B. Ambrosone, and S. E. McCann Consumption of Raw Cruciferous Vegetables is Inversely Associated with Bladder Cancer Risk Cancer Epidemiol. Biomarkers Prev., April 1, 2008; 17(4): 938 - 944. [Abstract] [Full Text] [PDF]

				R. Munday, P. Mhawech-Fauceglia, C. M. Munday, J. D. Paonessa, L. Tang, J. S. Munday, C. Lister, P. Wilson, J. W. Fahey, W. Davis, et al. Inhibition of Urinary Bladder Carcinogenesis by Broccoli Sprouts Cancer Res., March 1, 2008; 68(5): 1593 - 1600. [Abstract] [Full Text] [PDF]

				L. Tang, Y. Zhang, H. E. Jobson, J. Li, K. K. Stephenson, K. L. Wade, and J. W. Fahey Potent activation of mitochondria-mediated apoptosis and arrest in S and M phases of cancer cells by a broccoli sprout extract. Mol. Cancer Ther., April 1, 2006; 5(4): 935 - 944. [Abstract] [Full Text] [PDF]

				L. Tang and Y. Zhang Mitochondria are the primary target in isothiocyanate-induced apoptosis in human bladder cancer cells Mol. Cancer Ther., August 1, 2005; 4(8): 1250 - 1259. [Abstract] [Full Text] [PDF]