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Abstract Number: 3184
Allyl isothiocyanate suppresses in vitro proliferation of PC-3 and LNCaP human prostate cancer cells by inducing apoptosis and mediating G2/M arrest
Dong Xiao, Sanjay K. Srivastava, Yan Zeng, Pamela A. Hershberger, Candace S. Johnson, Donald L. Trump, Shivendra V. Singh, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Epidemiological studies have suggested that increased consumption of cruciferous vegetables, e.g., broccoli, cabbage etc., may be beneficial in reducing the risk for certain types of malignancies including prostate cancer.
The anti-neoplastic activity of cruciferous vegetables is believed to be due to isothiocyanate (ITC) class of chemicals that are derived from glucosinolates.
Many ITCs have been shown to prevent chemically induced cancers in experimental animals either by inhibiting carcinogen activation and/or by enhancing detoxification of the activated chemical carcinogens. In the present study, we demonstrate that allyl isothiocyanate (AITC), a naturally occurring member of the ITC family of phytochemicals, is a potent inhibitor of the proliferation of PC-3 (androgen-independent) and LNCaP (androgen-dependent) human prostate cancer cells in culture.
Proliferation of both cancer cells in culture was inhibited significantly by AITC treatment (24-h exposure) with an IC50 of about 15-17 ìM. On the other hand, proliferation of the normal prostate epithelial cell line (PrEC) was not affected by AITC at concentrations that were highly cytotoxic in cancer cells. AITC treatment (20 ìM for 24 h) arrested PC-3 as well as LNCaP cells in G2/M phase.
Western blot analysis of the lysates from control and treated cells revealed down-regulation of G2/M checkpoint proteins, including cdc25B, cdc-2, and cyclin-B1, upon exposure to AITC. Furthermore, exposure to AITC resulted in apoptotic cell death, determined by flow cytometric analysis of annexin V staining, in both cell lines in a dose-dependent manner.
However, the precise mechanism of the AITC-induced apoptosis in PC-3 and LNCaP cells remains to be established. In conclusion, the results of the present study indicate that AITC is an effective inhibitor of the proliferation of human prostate cancer cells in culture, and that the anti-proliferative activity of AITC against prostate cancer cells is due to G2/M cell cycle arrest and induction of apoptosis.
Therefore, it is reasonable to postulate that AITC, and possibly other members of the ITC family of natural phytochemicals, may find use, either singly or in combination with other anti-neoplastic agents in the prevention/treatment of human prostate cancer.
(Supported by NIH grants CA55589, CA91478 and CA76348).
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