Emerging evidence supports that prostate cancer originates from a rare subpopulation of cells, namely prostate cancer stem cells (CSCs). Conventional therapies for prostate cancer are believed to mainly target the majority of differentiated tumor cells but spare CSCs, which may account for the subsequent disease relapse after treatment. Therefore, successful elimination of CSCs may be an effective strategy to achieve complete remission from this disease. Gamma‐tocotrienols (γ‐T3) is one of the vitamin‐E constituents, which have been shown to have anticancer effects against a wide range of human cancers. Recently, we have reported that γ‐T3 treatment not only inhibits prostate cancer cell invasion but also sensitizes the cells to docetaxel‐induced apoptosis, suggesting that γ‐T3 may be an effective therapeutic agent against advanced stage prostate cancer. Here, we demonstrate for the first time that γ‐T3 can downregulate the expression of prostate CSC markers (CD133/CD44) in androgen‐independent prostate cancer cell lines (PC‐3 and DU145), as evident from Western blotting analysis. Meanwhile, the spheroid formation ability of the prostate cancer cells was significantly hampered by γ‐T3 treatment. In addition, pretreatment of PC‐3 cells with γ‐T3 was found to suppress tumor initiation ability of the cells. More importantly, although CD133‐enriched PC‐3 cells were highly resistant to docetaxel treatment, these cells were as sensitive to γ‐T3 treatment as the CD133‐depleted population. Our data suggest that γ‐T3 may be an effective agent in targeting prostate CSCs, which may account for its anticancer and chemosensitizing effects reported in previous studies.

cleaved caspase-3, were assessed by immunohistochemical staining. The inhibitory effects of SAC on prostate cancer invasion was examined by immunoreactivity of Ecadherin and its binding proteins α , β and γ -catenins. The serum prostate-specific antigen (PSA) level at three different times (initiation, middle and end of treatment) and toxicity of SAC on several organs after treatment were assessed. RESULTSTreatment with SAC resulted in inhibition of the growth of CWR22R, with no detectable toxic effect on nude mice. The SAC-induced growth reduction was correlated with a concurrent reduction in serum PSA level and proliferation rate of xenografts, together with an inhibition of invasion through the restoration of E-cadherin and γ -catenin expression. Furthermore, the apoptotic rate of SAC-treated tumours increased together with a decrease in Bcl-2 and increase in cleaved caspase-3. CONCLUSIONThese results suggest that this garlic-derived compound might be a potential therapeutic agent for suppressing AI prostate cancer.