Suppression of prostate cancer in a transgenic rat model via gamma-tocopherol activation of caspase signaling.
BACKGROUND
Epidemiological data indicate that intake of one form of vitamin E, gamma-tocopherol, may reduce prostate cancer risk, and several in vitro studies have demonstrated that gamma-tocopherol can inhibit prostate cancer cell growth. The purpose of the present study was to confirm effects of gamma-tocopherol on prostate cancer in the transgenic rat for adenocarcinoma of prostate (TRAP) model established in our laboratory.


METHODS
In Experiment 1, heterozygous male TRAP rats 5 weeks of age received alpha-tocopherol at the concentration of 50 mg/kg in the diet, or gamma-tocopherol at 50 or 100 mg/kg for 10 weeks. In Experiment 2, TRAP rats of 3 weeks of age were given gamma-tocopherol at 50, 100, or 200 mg/kg diet for 7 weeks.


RESULTS
gamma-Tocopherol did not affect body weight gain, organ weights or serum levels of either testosterone or estradiol. However, quantitative evaluation of prostatic lesions demonstrated significantly suppression of sequential progression from PIN to adenocarcinoma in a dose-dependent manner, along with clear activation of caspases 3 and 7 in the ventral lobe in both experiments.


CONCLUSIONS
The present study clearly demonstrated that gamma-tocopherol suppresses prostate tumor progression in an in vivo TRAP model, and could be a candidate chemopreventive agent for human prostate cancer.
Takahashi
Satoru
S
Department of Experimental Pathology and Tumor Biology, Mizuho-ku, Nagoya, Japan. sattak@med.nagoya-cu.ac.jp
Takeshita
Kentaro
K
Seeni
Azman
A
Sugiura
Satoshi
S
Tang
Mingxi
M
Sato
Shin-ya
SY
Kuriyama
Hiroki
H
Nakadate
Masao
M
Abe
Koichi
K
Maeno
Yoshitaka
Y
Nagao
Masataka
M
Shirai
Tomoyuki
T
D000135:Acid Phosphatase / Q000235:genetics; D000230:Adenocarcinoma / Q000188:drug therapy / Q000517:prevention & control*; D000818:Animals; D030801:Animals, Genetically Modified; D000975:Antioxidants / Q000627:therapeutic use; D002518:Ceramides / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D051381:Rats; D000071681:Tartrate-Resistant Acid Phosphatase; D024505:Tocopherols / Q000097:blood; D024504:gamma-Tocopherol / Q000627:therapeutic use*
D000975:Antioxidants; D002518:Ceramides; D007527:Isoenzymes; D024504:gamma-Tocopherol; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D024505:Tocopherols