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

Luk, Sze Ue, Yap, Wei Ney, Chiu, Yung-Tuen, Lee, Davy T.W., Ma, Stephanie, Lee, Terence Kin Wah, Vasireddy, Raja S., Wong, Yong-Chuan, Ching, Yick Pang, Nelson, Colleen C., Yap, Yee Leng, & Ling, Ming-Tat (2010) Gamma-tocotrienol as an effective agent in targeting prostate cancer stem cell-like population. International Journal of Cancer.

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Emerging evidence supports that prostate cancer originates from a rare sub-population 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 (-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 -T3 treatment not only inhibits prostate cancer cell invasion but also sensitizes the cells to docetaxel-induced apoptosis, suggesting that -T3 may be an effective therapeutic agent against advanced stage prostate cancer. Here, we demonstrate for the first time that -T3 can down-regulate the expression of prostate CSC markers (CD133/CD44) in androgen independent (AI) prostate cancer cell lines (PC-3 & DU145), as evident from western blotting analysis. Meanwhile, the spheroid formation ability of the prostate cancer cells was significantly hampered by -T3 treatment. In addition, pre-treatment of PC-3 cells with -T3 was found to suppress tumor initiation ability of the cells. More importantly, while CD133-enriched PC-3 cells were highly resistant to docetaxel treatment, these cells were as sensitive to -T3 treatment as the CD133-depleted population. Our data suggest that -T3 may be an effective agent in targeting prostate CSCs, which may account for its anticancer and chemosensitizing effects reported in previous studies.

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45 citations in Scopus
38 citations in Web of Science®
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ID Code: 34110
Item Type: Journal Article
Refereed: Yes
Keywords: vitamin E, stem cell, prostate cancer, Tocotrienol
DOI: 10.1002/ijc.25546
ISSN: 0020-7136
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200)
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
Past > Schools > Medical Sciences
Deposited On: 20 Aug 2010 00:43
Last Modified: 12 Oct 2015 04:52

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