Allyl isothiocyanate (
AITC), which occurs in many common cruciferous vegetables, was recently shown to be selectively delivered to
bladder cancer tissues through urinary excretion and to inhibit
bladder cancer development in rats. The present investigation was designed to test the hypothesis that
AITC-containing cruciferous vegetables also inhibit
bladder cancer development. We focused on an
AITC-rich mustard seed
powder (MSP-1).
AITC was stably stored as its
glucosinolate precursor (
sinigrin) in
MSP-1. Upon addition of water, however,
sinigrin was readily hydrolyzed by the accompanying endogenous
myrosinase. This
myrosinase was also required for full conversion of
sinigrin to
AITC in vivo, but the matrix of
MSP-1 had no effect on
AITC bioavailability.
Sinigrin itself was not bioactive, whereas hydrated
MSP-1 caused apoptosis and G(2)/M phase arrest in
bladder cancer cell lines in vitro. Comparison between hydrated
MSP-1 and pure
sinigrin with added
myrosinase suggested that the anticancer effect of
MSP-1 was derived principally, if not entirely, from the
AITC generated from
sinigrin. In an orthotopic rat
bladder cancer model, oral
MSP-1 at 71.5 mg/kg (
sinigrin dose of 9 μmol/kg) inhibited
bladder cancer growth by 34.5% (P < 0.05) and blocked muscle invasion by 100%. Moreover, the anticancer activity was associated with significant modulation of key
cancer therapeutic targets, including
vascular endothelial growth factor,
cyclin B1 and
caspase 3. On an equimolar basis, the anticancer activity of
AITC delivered as
MSP-1 appears to be more robust than that of pure
AITC.
MSP-1 is thus an attractive delivery vehicle for
AITC and it strongly inhibits
bladder cancer development and progression.