Epidemiological studies support the premise that dietary consumption of cruciferous vegetables may lower the risk of various malignancies, including prostate cancer. Anticancer effect of cruciferous vegetables is attributed to isothiocyanates (ITC) which are generated upon processing (cutting or chewing) of these vegetables. One of the ITCs shown to have chemopreventive properties is D,L-Sulforaphane (SFN). In the present study we hypothesized that SFN administration inhibits prostate cancer progression and metastasis in TRAMP mouse model. Oral administration of SFN reduced the incidence of prostatic intraepithelial neoplasia (PIN) and well-differentiated (WD) carcinoma in the dorsolateral prostate by 28% (P=0.006) and 23% (P=0.0104), respectively, in comparison with control mice. Additionally, the area occupied by the WD carcinoma was reduced by 44% (P= 0.0011) in SFN-treated mice as compared to the control group. SFN also reduced the PIN area in the dorsolateral prostate by about 24% compared to controls but the difference did not reach significance. Changes in the incidence and the area of the WD carcinoma were not caused by suppression of the T-antigen expression. SFN had the most striking impact on the incidence of pulmonary metastasis. In the control group metastasis was detected in ~80% of animals while only ~40% of SFN-treated mice had pulmonary metastasis. The multiplicity of pulmonary metastasis was ~63% lower (P=0.042) in SFN-treated group compared with control animals. SFN administration reduced cellular proliferation by 40% (P=0.028), as demonstrated by the PCNA, and increased apoptosis by 1.9 fold, as indicated by TUNEL staining. On the other hand, SFN treatment did not affect neo-angiogenesis or E-cadherin expression in the prostate/tumor tissue. Western blot analyses using prostate/tumor lysates revealed that SFN-treated animals had higher levels of pro-apoptotic Bcl-2 proteins, increased levels of cleaved PARP and decreased levels of anti-apoptotic proteins when compared to controls. In summary, results of this study indicate that SFN administration inhibits prostate cancer progression and development of pulmonary metastasis in TRAMP mice by reducing proliferation and increasing expression of pro-apoptotic proteins. This investigation was supported by US PHS grant CA115498, awarded by the National Cancer Institute.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2101.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO