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 (IC(50)) of 2.7-3.3 microM], which was associated with profound G(2)/M arrest and apoptosis. In contrast,
AITC was markedly less toxic to normal human bladder epithelial cells (IC(50) of 69.4 microM).
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.