Inhibition of bladder cancer development by allyl isothiocyanate.
Bladder cancer is one of the common human cancers and also has a very high recurrence rate. There is a great need for agents capable of inhibiting bladder cancer development and recurrence. Here, we report that allyl isothiocyanate (AITC), an ingredient of many common cruciferous vegetables, potently inhibited the proliferation of bladder carcinoma cell lines in vitro [half maximal inhibitory concentration (IC(50)) of 2.7-3.3 microM], which was associated with profound G(2)/M arrest and apoptosis. In contrast, AITC was markedly less toxic to normal human bladder epithelial cells (IC(50) of 69.4 microM). AITC was then evaluated in two rat bladder cancer models in vivo (an orthotopic model and a subcutaneous model). The orthotopic model closely mimics human bladder cancer development and recurrence. We show that a low oral dose of AITC (1 mg/kg) significantly inhibited the development and muscle invasion of the orthotopic bladder cancers but was ineffective against the subcutaneous xenografts of the same cancer cells in the same animals. This differential effect was explained by our finding that urinary levels of AITC equivalent were two to three orders of magnitude higher than that in the plasma and that its levels in the orthotopic cancer tissues were also three orders of magnitude higher than that in the subcutaneous cancer tissues. Moreover, we show that AITC is a multi-targeted agent against bladder cancer. In conclusion, AITC is selectively delivered to bladder cancer tissue through urinary excretion and potently inhibits bladder cancer development and invasion.
Bhattacharya
Arup
A
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Tang
Li
L
Li
Yun
Y
Geng
Feng
F
Paonessa
Joseph D
JD
Chen
Shang Chiung
SC
Wong
Michael K K
MK
Zhang
Yuesheng
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005520:Food Preservatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D017879:Isothiocyanates / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
D005520:Food Preservatives; D017879:Isothiocyanates; C004471:allyl isothiocyanate