Gamma-tocotrienol vs prostate stem cells

[Guest guest]

Int J Cancer. 2010 Jul 8. [Epub ahead of print]

Gamma-tocotrienol as an effective agent in targeting prostate cancer

stem cell-like population.

<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Luk%20SU%22%5BAuthor%5D>Luk

SU,

<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Yap%20WN%22%5BAuthor%5D>Yap

WN,

<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Chiu%20YT%22%5BAuthor%5D>Chiu

YT,

<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Lee%20DT%22%5BAuthor%5D>Lee

DT,

<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Ma%20S%22%5BAuthor%5D>Ma

S,

<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Lee%20TK%22%5BAuthor%5D>Lee

TK,

<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Vasireddy%20RS%22%5BAuthor%5D>Vasire\

ddy

RS,

<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Wong%20YC%22%5BAuthor%5D>Wong

YC,

<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Ching%20YP%22%5BAuthor%5D>Ching

YP,

<http://www.ncbi.nlm.nih.gov/pubmed?term=%22%20C%22%5BAuthor%5D>

C,

<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Yap%20YL%22%5BAuthor%5D>Yap

YL,

<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Ling%20MT%22%5BAuthor%5D>Ling MT.

Department of Anatomy, the University of Hong Kong, Hong Kong, SAR, China.

Abstract

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 (gamma-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 gamma-T3 treatment

not only inhibits prostate cancer cell invasion but also sensitizes

the cells to docetaxel-induced apoptosis, suggesting that gamma-T3

may be an effective therapeutic agent against advanced stage prostate

cancer. Here, we demonstrate for the first time that gamma-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 gamma-T3 treatment. In addition, pre-treatment of PC-3

cells with gamma-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 gamma-T3 treatment as the CD133-depleted population. Our

data suggest that gamma-T3 may be an effective agent in targeting

prostate CSCs, which may account for its anticancer and

chemosensitizing effects reported in previous studies.