We have previously shown that broccoli sprouts are a rich source of chemopreventive isothiocyanates (ITCs), which potently induce carcinogen-detoxifying enzymes and inhibit the development of mammary and skin tumors in rodents. However, the principal ITC present in broccoli sprout extracts, sulforaphane (SF), not only induces carcinogen-detoxifying enzymes but also activates apoptosis and blocks cell cycle progression. In the present report we show that an aqueous extract of broccoli sprouts potently inhibits the growth of human bladder carcinoma cells in culture and that this inhibition is almost exclusively due to the ITCs. ITCs are present in broccoli sprouts as their glucosinolate precursors, and blocking their conversion to ITCs abolishes the antiproliferative activity of the extract. Moreover, the potency of ITCs in the extract in inhibiting cancer cell growth was almost identical to that of synthetic SF, as judged by their IC50 values (6.6 vs 6.8 μmol/L), suggesting that other ITCs in the extract may be biologically similar to SF and that non-ITC substances in the extract may not interfere with the antiproliferative activity of the ITCs. Further study showed that the ITC extract of broccoli sprouts activated the mitochondria-mediated apoptosis pathway and halted cells in S and M phases. Cell cycle arrest was associated with down-regulation of cell division cycle 25C and disruption of mitotic spindles. These data show that broccoli sprout ITC extract is a highly promising substance for cancer prevention/treatment, and that its antiproliferative activity is exclusively derived from ITCs. Supported by National Cancer Institute grant CA100623.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]