ABSTRACT
Over the last two decades, an enormous amount of scienti•c effort has been devoted to studying the relationship between vitamin E and prostate cancer. This effort is well justi•ed, since prostate cancer remains the most common cancer in American men after skin cancer and is the second leading cause of cancer deaths: over 220,000 men will develop prostate each year (U.S. Cancer Statistics Working Group 2011). Nevertheless, large-scale, well-designed clinical intervention studies have not shown that alpha-tocopherol prevents prostate cancer or cancer in
8.1 Introduction .......................................................................................................................... 101 8.2Vitamin E Is Both Tocopherols and Tocotrienols................................................................ 102
8.2.1 Vitamin E Isoforms Have Distinct Chemical, Biological, and Anticancer Properties .....102 8.2.2Tocotrienols, but Not Tocopherols, Are Farnesylated Benzopyrans and Have
Unique Effects on Isoprenoid and Cholesterol Synthesis......................................... 104 8.2.3 Alpha-Tocopherol Can Interfere with the Anticancer Effects of Tocotrienols ......... 104
8.3Tocotrienols and Targeted Chemoprevention for Prostate Cancer....................................... 105 8.3.1High Level of Low-Density Lipoprotein-Cholesterol Is a Risk Factor
for Prostate Cancer................................................................................................... 106 8.3.2Men Taking a Statin for High LDL-Cholesterol Would Likely Respond
to Tocotrienol Chemoprevention for Prostate Cancer .............................................. 106 8.3.3High-Grade Prostatic Intraepithelial Neoplasia as a Surrogate Endpoint
Biomarker for Prostate Cancer................................................................................. 106 8.4Tocotrienols and Prostate Cancer Molecular and Cellular Targets...................................... 107
8.4.1High-Grade Prostatic Intraepithelial Neoplasia, Tocotrienols, and the TRAMP Animal Model ............................................................................... 107
8.4.2Practical Aspects of Tocotrienol Supplementation................................................... 107 8.4.3Molecular Mechanisms Underlying the Chemopreventive
Effects of Tocotrienols in Prostate Cancer............................................................... 108 8.4.4Cholesterol, Lipid Rafts, and Prostate Cancer......................................................... 108 8.4.5 Akt1 and Lipid Rafts in Prostate Cancer Cells ........................................................ 109 8.4.6 Tocotrienols and Statins Affect the Isoprenylation of G-Protein Regulatory Proteins ....109
