Gamma-tocotrienol as an effective agent in targeting prostate cancer stem cell-like population

Sze Ue Luk¹, Wei Ney Yap₂, Yung-Tuen Chiu¹, Davy TW Lee¹, Stephanie Ma³, Terence Kin Wah Lee³, Raja S Vasireddy⁴, Yong-Chuan Wong¹, Yick Pang Ching¹, Colleen Nelson⁴, Yee Leng Yap² and Ming-Tat Ling⁴
¹Department of Anatomy, Faculty of Medicine, the University of Hong Kong, Hong Kong, SAR, China
²Davos Life Science, Pvt., Ltd., Cancer Research Laboratory, the Helios, Singapore
³Department of Pathology, Faculty of Medicine, the University of Hong Kong, Hong Kong, SAR, China
⁴Australian Prostate Cancer Research Centre, Queensland & Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia

Int. J. Cancer: 128, 2182–2191 (2011) CV 2010 UICC
DOI: 10.1002/ijc.25546
Accepted 17 Jun 2010; Online 8 Jul 2010

Abstract:

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 (c-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 c-T3 treatment not only inhibits prostate cancer cell invasion but also sensitizes the cells to docetaxel-induced apoptosis, suggesting that c-T3 may be an effective therapeutic agent against advanced stage prostate cancer. Here, we demonstrate for the first time that c-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 c-T3 treatment. In addition, pretreatment of PC-3 cells with c-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 c-T3 treatment as the CD133-depleted population. Our data suggest that c-T3 may be an effective agent in targeting prostate CSCs, which may account for its anticancer and chemosensitizing effects reported in previous studies.

Keywords:

Tocotrienol, prostate cancer, stem cell, vitamin E