tocotrienol--delta and ferulic-acid

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 δ-T3 on angiogenesis and telomerase activity. In this study, we examined the synergistic suppressive effects of the combination of δ-T3 and FA on telomerase activity in DLD-1 human colorectal adenocarcinoma cells. Co-treatment with δ-T3 and FA significantly decreased cellular telomerase activity compared to treatment with δ-T3 alone, whereas FA alone had no inhibitory effect. Co-treatment with δ-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 δ-T3, suggesting that FA improved the bioavailability of δ-T3, thereby increasing the inhibitory potency of δ-T3 on telomerase. FA may be a promising candidate for augmenting the anti-cancer activity of δ-T3.

Topics: Adenocarcinoma; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Coumaric Acids; Down-Regulation; Drug Synergism; Humans; Telomerase; Vitamin E

Rice bran consists of many functional compounds and thus much attention has been focused on the health benefits of its components. Here, we investigated the synergistic inhibitory effects of its components, particularly δ-tocotrienol (δ-T3) and ferulic acid (FA), against the proliferation of an array of cancer cells, including DU-145 (prostate cancer), MCF-7 (breast cancer), and PANC-1 (pancreatic cancer) cells. The combination of δ-T3 and FA markedly reduced cell proliferation relative to δ-T3 alone, and FA had no effect when used alone. Although δ-T3 induced G1 arrest by up-regulating p21 in PANC-1 cells, more cells accumulated in G1 phase with the combination of δ-T3 and FA. This synergistic effect was attributed to an increase in the cellular concentration of δ-T3 by FA. Our results suggest that the combination of δ-T3 and FA may present a new strategy for cancer prevention and therapy.

Topics: Cell Line, Tumor; Cell Proliferation; Coumaric Acids; Drug Synergism; Humans; Neoplasms; Real-Time Polymerase Chain Reaction; Vitamin E