A Combination of δ-Tocotrienol and Ferulic Acid Synergistically Inhibits Telomerase Activity in DLD-1 Human Colorectal Adenocarcinoma Cells

Rice bran is a rich source of functional compounds, including tocotrienol (T3) and ferulic acid (FA). We previously investigated the anti-cancer properties of T3, and reported on the potent inhibitory effects of delta-T3 on angiogenesis and telomerase activity. In this study, we examined the synergistic suppressive effects of the combination of delta-T3 and FA on telomerase activity in DLD-1 human colorectal adenocarcinoma cells. Co-treatment with delta-T3 and FA significantly decreased cellular telomerase activity compared to treatment with delta-T3 alone, whereas FA alone had no inhibitory effect. Co-treatment with delta-T3 and FA also synergistically down-regulated the expression of human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, indicating that the enzymatic activity of telomerase is controlled at the transcriptional level. FA significantly increased the intracellular concentration of delta-T3, suggesting that FA improved the bioavailability of delta-T3, thereby increasing the inhibitory potency of delta-T3 on telomerase. FA may be a promising candidate for augmenting the anti-cancer activity of delta-T3.