Combination Effect of δ-Tocotrienol and γ-Tocopherol on Prostate Cancer Cell Growth

Tocotrienols (T3s) and tocopherols (Tocs) are both members of the vitamin E family. It is known that delta-tocotrienol (delta-T3) has displayed the most potent anti-cancer activity amongst the tocotrienols. On the other hand, gamma-tocopherol (gamma-Toc) is reported to have a protective effect against prostate cancer. Therefore, we investigated whether the combination of gamma-Toc and delta-T3 could strengthen the inhibitory effect of delta-T3 on prostate cancer cell growth. In this study the effect of combined delta-T3 (annatto T3 oil) and gamma-Toc (Tmix, delta-Toc-rich oil) therapy was assessed against human androgen-dependent prostate cancer cells (LNCaP). We found that combined treatment of delta-T3 (10 mu M) and gamma-Toc (5 mu M) resulted in reinforced anti-prostate cancer activity. Specifically, cell cycle phase distribution analysis revealed that in addition to G1 arrest caused by the treatment with delta-T3, the combination of delta-T3 with g-Toc induced G2/M arrest. Enhanced induction of apoptosis by the combined treatment was also observed. These findings indicate that combination of delta-T3 and gamma-Toc significantly inhibits prostate cancer cell growth due to the simultaneous cell cycle arrest in the G1 phase and G2/M phase.