Vitamin E inhibits the high-fat diet promoted growth of established human prostate LNCaP tumors in nude mice

Purpose: Prostate cancer has become an important public health problem in the Western world. It is currently the most common diagnosed cancer and the second leading cause of cancer deaths among North American men. Prostate cancer possesses a unique descriptive epidemiology which suggests that environmental factors (such as dietary fat consumption) play a pivotal role in tumor progression. Data from our institution have demonstrated that diets high in fat content can accelerate the growth of human LNCaP prostate cancer cells. One of the hypothesized mechanisms of dietary fat induced growth is oxidative stress. Our purpose was to determine the effect of supplemental Vitamin E, a potent intracellular antioxidant, on the high-fat promoted growth of transplanted LNCaP cells in the athymic mouse. Materials and Methods: Tumors were induced by subcutaneous injection of 10(6) LNCaP cells. Mice were fed a control diet consisting of 40.5% of total calories from dietary fat. Once tumors were formed, PSA values were obtained and animals were randomized into 4 groups of 12. The animals were then assigned to one of 4 dietary plans. Group 1 received the control diet of 40.5%-kcal fat. Group 2 received the 40.5%-kcal fat diet plus supplemental Vitamin E. Group 3 received a diet of 21.2%-kcal fat. Group 4 received the 21.2%-kcal fat diet plus supplemental Vitamin E. Food intake, animal weights, and, tumor volumes were recorded weekly. Survival analyses with time to a target volume of 0.523 cm.(3) (defined as failure) were used to compare tumor growth among the 4 groups. Two-sided tests (log rank test) with a set at 0.05 were used to determine significance. Results: tumor growth rates were highest in the animals fed a 40.5%-kcal fat diet (p < 0.05 group 1). Tumors in animals fed 40.5%-kcal fat plus Vitamin E, 21.2%-kcal fat, and 21.2%-kcal fat plus Vitamin E, experienced statistically indistinguishable growth rates. No significant differences were noted in total ingested calories, animal weight gain or initial PSA levels. Conclusions: These data suggest that the mechanism of dietary fat induced growth of human prostate cancer cells is mediated by oxidative stress. It also raises the possibility of a therapeutic benefit of vitamin E in preventing prostate cancer.