Gamma-tocopherol-enriched mixed tocopherol diet inhibits prostate carcinogenesis in TRAMP mice.
Gamma-tocopherol (gamma-T) alone or in combination with alpha-tocopherol has been shown to suppress biomarkers of oxidative stress in asthamatics and human subjects with metabolic syndrome. Oxidative stress has been implicated as a key event in prostate carcinogenesis. Hence, the purpose of this study was to examine the effects of gamma-tocopherol-enriched mixed tocopherol diet on prostate carcinogenesis in a murine prostate cancer model (TRAMP). 8 week old TRAMP males were fed 0.1% gamma-T-enriched mixed tocopherol diet that contained 20-fold higher levels of gamma-tocopherol, and roughly 3-fold higher levels of alpha-tocopherol. The effect of such diet on tumor and PIN development was observed. The expression of phase II detoxifying, antioxidant enzymes and Nrf2 mRNA and protein were determined by RT-PCR, immunohistochemistry and western blotting techniques. Treatment with gamma-T-enriched mixed tocopherols significantly suppressed the incidence of palpable tumor and Prostate Intraepithelial Neoplasia (PIN) development without affecting the expression of the transgene (SV-40). Tumor progression occurred with a significant suppression of antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase, heme-oxygenase-1 and phase II detoxifying enzymes. Treatment with gamma-T-enriched mixed tocopherol diet upregulated the expression of most detoxifying and antioxidant enzymes. Nrf2-a redox sensitive transcription factor known to mediate the expression of phase II detoxifying enzymes, was also significantly upregulated following treatment with gamma-T-enriched mixed tocopherol diet. Gamma-T-enriched mixed tocopherols significantly up-regulated the expression of Nrf2 and its related detoxifying and antioxidant enzymes thereby suppressing PIN and tumor development.
Barve
Avantika
A
Graduate Program in Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Khor
Tin Oo
TO
Nair
Sujit
S
Reuhl
Kenneth
K
Suh
Nanjoo
N
Reddy
Bandaru
B
Newmark
Harold
H
Kong
Ah-Ng
AN
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western; D004032:Diet; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D050217:Metabolic Detoxication, Phase II; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000178:diet therapy* / Q000517:prevention & control*; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D024505:Tocopherols / Q000627:therapeutic use*; D024504:gamma-Tocopherol / Q000627:therapeutic use*
D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D012313:RNA; D024504:gamma-Tocopherol; D010088:Oxidoreductases; D024505:Tocopherols