Isothiocyanates in the chemoprevention of bladder cancer

Development of effective preventive strategies for bladder cancer is of critical importance. Bladder cancer is ;among the most common human malignancies and typically recurs after treatment. Many plant-derived isothiocyanates (ITCs) have shown cancer-preventive activity in a variety of rodent organs. They arc known to inhibit carcinogen-activating enzymes. and to induce carcinogen-detoxifying enzymes, apoptosis. cell cycle arrest, and differentiation of cancer cells. More importantly, orally ingested ITCs Lire efficiently absorbed. rapidly and almost exclusively excreted and concentrated in the urine as N-acetylcysteine conjugates (NAC-ITC). NAC-ITCs also possess anticarcinogenic activity perhaps due largely to their facile dissociation to Free ITCs. Storage of urine in the bladder makes the bladder epithelium. which lines the inner surface Of the bladder and gives rise to the majority of bladder cancers, the most exposed tissue to ITCs/NAC-ITCs upon their ingestion. Storage of urine in the bladder also will increase file release of ITCs from NAC-ITCs. Consequently. the amount of ITCs needed orally to achieve cancer prevention in the bladder may be much lower than that required for other organs. As a result, potential systemic adverse effects of ITCs may be minimized When using ITCs for chemoprevention of bladder carcinogenesis. Taken to ether, ITCs may be especially useful for the prevention of bladder cancer.