Abstract A73: Bladder cancer inhibition by allyl isothiocyante

Nearly all cancers of the urinary bladder originate from its inner surface (epithelium). While most bladder cancers are diagnosed at an early stage, recurrence rate is extremely high. There is an urgent need for agents capable of inhibiting bladder cancer development and recurrence. Allyl isothiocyanate (AITC), an ingredient of many common cruciferous vegetables, was previously shown to kill bladder cancer cells in vitro. Our objective was to evaluate the chemopreventive potential of AITC against bladder cancer. The anticancer activities of AITC were assessed using multiple bladder cancer cell lines in vitro and two rat bladder cancer models in vivo (an orthotopic model and a subcutaneous model). Its toxicity toward normal human bladder epithelial (NHBE) cells was also examined. Pharmacokinetic study of AITC and histological examination of normal and malignant bladder tissues of AITC‐treated rats were undertaken as well. Proliferation of bladder cancer cells was potently inhibited by AITC (IC 50 of approximately 3 µM), which was associated with G2/M arrest and apoptosis. AITC was markedly less toxic to NHBE cells (IC 50 of 69 µM). Low oral dose of AITC (1 mg/kg), starting one day after cancer cell inoculation significantly inhibited the development of orthotopic bladder cancer, but was ineffective against subcutaneous xenografts of the same cancer cells. This differential effect was explained by our finding that urinary concentrations of AITC equivalent were 2–3 orders of magnitude higher than that in the plasma, and that its levels in the orthotopic bladder cancer tissues were also 3 orders of magnitude higher than that in the subcutaneous cancer tissues. Thus, AITC is selectively delivered to bladder cancer tissue through urinary excretion and potently inhibits bladder cancer development in vivo. Besides its potential use for prevention of primary bladder cancer, AITC appears to represent a novel and very attractive approach in the management of recurrence of superficial bladder cancer, since all currently available intravesicle therapies against bladder cancer recurrence mandate urethral catherization. In addition, this new knowledge opens the possibility for adjuvant or multimodality combination approaches for the prevention and treatment of bladder cancer. Supported by NCI grant CA124627. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A73.