d-Tocotrienol is the Most Potent Vitamin E Form in Inhibiting Prostate Cancer Cell Growth and Inhibits Prostate Carcinogenesis in Pten^p-/- Mice

Vitamin E compounds, consisting of a, b, g, and d forms of tocopherols and tocotrienols, display different cancer preventive activities in experimental models. Tocotrienols may have higher potential for clinical use due to their lower effective doses in laboratory studies. However, most studies on tocotrienols have been carried out using cancer cell lines. Strong data from animal studies may encourage the use of tocotrienols for human cancer prevention research. To examine the cancer inhibitory activity of different vitamin E forms, we first investigated their inhibitory activities of different vitamin E forms in prostate cancer cell lines. We found that d-tocotrienol (dT3) was the most effective form in inhibiting cell growth at equivalent doses. Because of this in vitro potency, dT3 was further studied using prostate-specific Pten^-/-(Pten^p-/-) mice. We found that 0.05% dT3 in diet reduced prostate adenocarcinoma multiplicity by 32.7%, featuring increased apoptosis and reduced cell proliferation. The inhibitory effect of 0.05% dT3 in diet was similar to that of 0.2% d-tocopherol (dT) in diet reported previously. Our further study on the dT3-induced transcriptome changes indicated that dT3 inhibited genes in blood vessel development in the prostate of Pten^p-/- mice, which was confirmed by IHC. Together, our results demonstrate that dT3 effectively inhibits the development of prostate adenocarcinoma in Pten^p-/- mice, which involves inhibition of proliferation and angiogenesis and promotion of apoptosis.