title: Mixed tocotrienols inhibit prostate carcinogenesis in TRAMP mice.
abstract: The biological activities of tocotrienols are receiving increasing attention. Herein, we report the efficacy of a mixed-tocotrienol diet against prostate tumorigenesis in the transgenic adenocarcinoma mouse prostate (TRAMP) mouse model. Male TRAMP mice, 8 wk old, were fed 0.1%, 0.3%, or 1% mixed tocotrienols in AIN-76A diet up to 24 wk old. Likewise, a positive control group consisting of male TRAMP mice and a negative control group consisting of wild-type nontransgenic mice were fed regular AIN-76A diet up to 24 wk old. Our results show that mixed-tocotrienol-fed groups had a lower incidence of tumor formation along with a significant reduction in the average wet weight of genitourinary apparatus. Furthermore, mixed tocotrienols significantly reduced the levels of high-grade neoplastic lesions as compared to the positive controls. This decrease in levels of high-grade neoplastic lesions was found to be associated with increased expression of proapoptotic proteins BAD (Bcl(2) antagonist of cell death) and cleaved caspase-3 and cell cycle regulatory proteins cyclin dependent kinase inhibitors p21 and p27. In contrast, the expression of cyclins A and E were found to be decreased in mixed-tocotrienol groups. Taken together, our results show that by modulating cell cycle regulatory proteins and increasing expression of proapoptotic proteins, mixed tocotrienols suppress prostate tumorigenesis in the TRAMP mice.
authors.affiliation: Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
authors.forename: Avantika
authors.initials: A
authors.lastname: Barve
authors.forename: Tin Oo
authors.initials: TO
authors.lastname: Khor
authors.forename: Kenneth
authors.initials: K
authors.lastname: Reuhl
authors.forename: Bandaru
authors.initials: B
authors.lastname: Reddy
authors.forename: Harold
authors.initials: H
authors.lastname: Newmark
authors.forename: Ah-Ng
authors.initials: AN
authors.lastname: Kong
mesh_terms: D000230:Adenocarcinoma / Q000517:prevention & control*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D024508:Tocotrienols / Q000008:administration & dosage*
chemical_list: D016588:Anticarcinogenic Agents; D024508:Tocotrienols