Gamma-tocotrienol as an effective agent in targeting prostate cancer stem cell-like population.
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.
Luk
Sze Ue
SU
Department of Anatomy, Faculty of Medicine, University of Hong Kong, Hong Kong, SAR, China.
Yap
Wei Ney
WN
Chiu
Yung-Tuen
YT
Lee
Davy T W
DT
Ma
Stephanie
S
Lee
Terence Kin Wah
TK
Vasireddy
Raja S
RS
Wong
Yong-Chuan
YC
Ching
Yick Pang
YP
Nelson
Colleen
C
Yap
Yee Leng
YL
Ling
Ming-Tat
MT
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002839:Chromans / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D002839:Chromans; D014810:Vitamin E; C013649:plastochromanol 8