Carcinogenesis Advance Access originally published online on March 28, 2003
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Carcinogenesis, Vol. 24, No. 5, 891-897,
May 2003
© 2003 Oxford University Press
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION |
Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits proliferation of human prostate cancer cells by causing G2/M arrest and inducing apoptosis
Departments of Pharmacology and Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
2 To whom correspondence should be addressed Email: singhs{at}msx.upmc.edu
Dietary isothiocyanates (ITCs) are highly effective in affording protection against chemically induced cancers in laboratory animals. In the present study, we demonstrate that allyl isothiocyanate (AITC), a constituent of cruciferous vegetables, significantly inhibits proliferation of cultured PC-3 (androgen-independent) and LNCaP (androgen-dependent) human prostate cancer cells in a dose-dependent manner with an IC50 of 
15–17 µM. On the other hand, survival of a normal prostate epithelial cell line (PrEC) was minimally affected by AITC even at concentrations that were highly cytotoxic to the prostate cancer cells. Reduced proliferation of PC-3 as well as LNCaP cells in the presence of AITC correlated with accumulation of cells in G2/M phase and induction of apoptosis. In contrast, AITC treatment failed to induce apoptosis or cause G2/M phase arrest in PrEC cells. A 24 h treatment of PC-3 and LNCaP cells with 20 µM AITC caused a significant decrease in the levels of proteins that regulate G2/M progression, including Cdk1 (32–50% reduction), Cdc25B (44–48% reduction) and Cdc25C (>90% reduction). A significant reduction in the expression of cyclin B1 protein (45%) was observed only in LNCaP cells. A 24 h exposure of PC-3 and LNCaP cells to an apoptosis-inducing concentration of AITC (20 µM) resulted in a significant decrease (31–68%) in the levels of anti-apoptotic protein Bcl-2 in both cell lines, and 58% reduction in Bcl-XL protein expression in LNCaP cells. In conclusion, it seems reasonable to hypothesize that AITC, and possibly other ITCs, may find use in the treatment of human prostate cancers.
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