Mixed tocotrienols inhibit prostate carcinogenesis in TRAMP mice

Avantika Barve, Tin Oo Khor, Kenneth Reuhl, Bandaru Reddy, Harold Newmark, Ah Ng Kong

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

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 (Bcl2 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.

Original languageEnglish (US)
Pages (from-to)789-794
Number of pages6
JournalNutrition and Cancer
Volume62
Issue number6
DOIs
StatePublished - Aug 2010

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research

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