Potent activation of mitochondria-mediated apoptosis and arrest in S and M phases of cancer cells by a broccoli sprout extract

Abstract

We have previously shown that broccoli sprouts are a rich source of chemopreventive isothiocyanates, which potently induce carcinogen-detoxifying enzymes and inhibit the development of mammary and skin tumors in rodents. However, the principal isothiocyanate present in broccoli sprout extracts, sulforaphane, not only induces carcinogen-detoxifying enzymes but also activates apoptosis and blocks cell cycle progression. In this article, 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 isothiocyanates. Isothiocyanates are present in broccoli sprouts as their glucosinolate precursors and blocking their conversion to isothiocyanates abolishes the antiproliferative activity of the extract. Moreover, the potency of isothiocyanates in the extract in inhibiting cancer cell growth was almost identical to that of synthetic sulforaphane, as judged by their IC 50 values (6.6 versus 6.8 Mmol/L), suggesting that other isothiocyanates in the extract may be biologically similar to sulforaphane and that nonisothiocyanate substances in the extract may not interfere with the antiproliferative activity of the isothiocyanates. Further study showed that the isothiocyanate extract of broccoli sprouts activated the mitochondriamediated apoptosis pathway and halted cells in S and M phases. Cell cycle arrest was associated with downregulation of Cdc25C and disruption of mitotic spindles. These data show that broccoli sprout isothiocyanate extract is a highly promising substance for cancer prevention/treatment and that its antiproliferative activity is exclusively derived from isothiocyanates. [Mol Cancer Ther 2006;5(4):935-44]

Inhibition of Urinary Bladder Carcinogenesis by Broccoli Sprouts

“…4B). These concentrations are tens-to hundreds-fold higher than that required for isothiocyanates and their dithiocarbamates metabolites to exert chemopreventive activity in cultured bladder cells, as shown in our previous studies (13,18,27). It remains to be determined if lower urinary concentrations of isothiocyanate equivalents in vivo are effective for bladder cancer prevention.…”

“…Thus, induction of both enzymes by the extract in the bladder seems to correlate with inhibition of bladder carcinogenesis, suggesting that induction of these enzymes may play a role and/or act as a reliable biomarker in the inhibition of bladder carcinogenesis by broccoli sprout extract. Broccoli sprout extract and sulforaphane have also been shown to induce apoptosis and cell cycle arrest in cultured bladder cancer cells (13,27,28), and were also shown to inhibit angiogenesis and cancer metastasis in nonbladder systems (29)(30)(31)(32). Whether any of these mechanisms contribute significantly to the chemopreventive effect of broccoli sprout extract in the present model is uncertain, because the extract was administered only in the initiation phase.…”

“…Broccoli sprouts are a very rich source of isothiocyanates, the majority of which is sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane], a highly promising cancer chemopreventive agent (11), with smaller amounts of two close sulforaphane analogues, iberin and erucin (12,13). These compounds are stored in plants in a stable precursor form (glucosinolates) and are generated through enzymatic hydrolysis of the latter substances by endogenous myrosinase, which is released when plant cells are disrupted.…”

“…N-acetylcysteine conjugate of sulforaphane was synthesized as previously described (18). Lyophilized broccoli sprout extract was prepared from 3-day-old broccoli sprouts, analyzed for isothiocyanate content, and stored at À70jC before use as previously described (13). Each gram of extract contained 140 Amol isothiocyanates, of which 70%, 25%, and 5% were sulforaphane, iberin, and erucin, respectively, with no glucosinolate remaining.…”

Green Synthesis of Selenium Nanoparticles from Broccoli, Characterization, Application and Toxicity

“…These phytochemicals are responsible for the induction of phase-2 detoxication enzymes as well as other antioxidant activities [19,20]. The phytochemicals in broccoli have recently gathered great interest in their potential for the maintenance of human health.…”