δ-Tocotrienol is the Most Potent Vitamin E Form in Inhibiting Prostate Cancer Cell Growth and Inhibits Prostate Carcinogenesis in Ptenp-/- Mice

Vitamin E compounds, consisting of alpha, beta, gamma, and delta 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 delta-tocotrienol (delta T3) was the most effective form in inhibiting cell growth at equivalent doses. Because of this in vitro potency, delta T3 was further studied using prostate-specific Pten(-/-) (Pten(p-/-)) mice. We found that 0.05% delta T3 in diet reduced prostate adenocarcinoma multiplicity by 32.7%, featuring increased apoptosis and reduced cell proliferation. The inhibitory effect of 0.05% delta T3 in diet was similar to that of 0.2% delta-tocopherol (delta T) in diet reported previously. Our further study on the delta T3-induced transcriptome changes indicated that delta T3 inhibited genes in blood vessel development in the prostate of Pten(p-/-) mice, which was confirmed by IHC. Together, our results demonstrate that delta T3 effectively inhibits the development of prostate adenocarcinoma in Pten(p-/-) mice, which involves inhibition of proliferation and angiogenesis and promotion of apoptosis. Prevention Relevance: We demonstrated that delta-tocotrienol is the most active vitamin E form in inhibiting the growth of several prostate cancer cell lines. In transgenic Pten(p)(-/-) mice, delta-tocotrienol inhibited the formation of prostate cancer. This result would encourage and help design clinical studies for the application of delta-tocotrienol for prostate cancer prevention.

Automated summary

The study found that delta-tocotrienol is the most effective form of vitamin E in inhibiting the growth of prostate cancer cell lines and in transgenic mice. This result has significant implications for the design of clinical studies on prostate cancer prevention.