Journal Article

Inhibition of bladder cancer development by allyl isothiocyanate

Arup Bhattacharya, Li Tang, Yun Li, Feng Geng, Joseph D. Paonessa, Shang Chiung Chen, Michael K.K. Wong and Yuesheng Zhang

in Carcinogenesis

Volume 31, issue 2, pages 281-286
Published in print February 2010 | ISSN: 0143-3334
Published online December 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp303
Inhibition of bladder cancer development by allyl isothiocyanate

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Bladder cancer is one of the common human cancers and also has a very high recurrence rate. There is a great need for agents capable of inhibiting bladder cancer development and recurrence. Here, we report that allyl isothiocyanate (AITC), an ingredient of many common cruciferous vegetables, potently inhibited the proliferation of bladder carcinoma cell lines in vitro [half maximal inhibitory concentration (IC50) of 2.7–3.3 μM], which was associated with profound G2/M arrest and apoptosis. In contrast, AITC was markedly less toxic to normal human bladder epithelial cells (IC50 of 69.4 μM). AITC was then evaluated in two rat bladder cancer models in vivo (an orthotopic model and a subcutaneous model). The orthotopic model closely mimics human bladder cancer development and recurrence. We show that a low oral dose of AITC (1 mg/kg) significantly inhibited the development and muscle invasion of the orthotopic bladder cancers but was ineffective against the subcutaneous xenografts of the same cancer cells in the same animals. This differential effect was explained by our finding that urinary levels of AITC equivalent were two to three orders of magnitude higher than that in the plasma and that its levels in the orthotopic cancer tissues were also three orders of magnitude higher than that in the subcutaneous cancer tissues. Moreover, we show that AITC is a multi-targeted agent against bladder cancer. In conclusion, AITC is selectively delivered to bladder cancer tissue through urinary excretion and potently inhibits bladder cancer development and invasion.

Journal Article.  5196 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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