Alpha-tocopheryl succinate (α-TOS) modulates human prostate LNCaP xenograft growth and gene expression in BALB/c nude mice fed two levels of dietary soybean oil

Background Malignancy of the prostate constitutes a leading cause of cancer-related deaths in America and Europe. Alpha-tocopheryl succinate (alpha-TOS) has been shown to inhibit human prostate cancer growth in vitro, via several mechanisms, including inhibiting prostate-specific antigen (PSA) and vascular endothelial growth factor (VEGF) expressions. The route of alpha-TOS administration has a profound effect on its antitumor activity, and few studies have investigated its effects on prostate cancer growth in vivo. Aim of the Study The present study tested the hypothesis that alpha-TOS wil reduce the growth of human prostate LNCaP tumors in mice fed low (7%) and high (20%) levels of dietary soybean oil, compared to the controls receiving vehicle, by modulating PSA and VEGF gene expressions in the tumor tissue. Methods BALB/c nude mice (n = 42) were subcutaneously inoculated with 1 x 10(6) LNCaP cells and assigned to one of four dietary groups; 7% or 20% soybean oil diet with or without alpha-TOS treatment. Three weeks later, mice received daily intraperitoneal injections of alpha-TOS (100 mg/kg body weight) in sesame seed oil (SSO) for two weeks; controls received SSO injections. Tumor volumes were recorded weekly. Sera, liver, and tumor tissues were collected at seven weeks for serum PSA, testosterone and alpha-tocopherol analyses, histopathological examination, and reverse transcription and polymerase chain reaction (RT-PCR) amplification of PSA and VEGF gene fragments in tumors. Relative quantification of gene expression was performed using real-time PCR. P <= 0.05 was considered significant. Results Intraperitoneal injections of alpha-TOS caused decreased tumor growth in both groups (7% and 20% fat, P < 0.05), versus controls. alpha-TOS treatment significantly reduced serum PSA and testosterone levels in comparison to the SSO-treated controls (P < 0.05). Control tumors had a greater degree of angiogenesis than alpha-TOS tumors, as demonstrated by the greater number of blood-filled vessels. PSA and VEGF mRNA expressions, were also reduced with alpha-TOS treatment (P < 0.05), revealing the possible molecular mechanisms of growth inhibition of LNCaP xenografts by alpha-TOS. Conclusions Our study shows significant reduction in LNCaP xenograft growth with alpha-TOS treatment in nude mice fed a low (7%) and high (20%) fat soybean oil diets versus controls. Serum PSA and testosterone, tumor angiogenesis, and PSA and VEGF mRNA expressions were markedly reduced by alpha-TOS administration, suggesting a possible role of alpha-TOS as a chemotherapeutic agent in human prostate cancer, and warrants further investigations on the dose and delivery of alpha-TOS in humans.