title: A Combination of δ-Tocotrienol and Ferulic Acid Synergistically Inhibits Telomerase Activity in DLD-1 Human Colorectal Adenocarcinoma Cells.
abstract: 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.
authors.affiliation: Faculty of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Eitsuka
authors.forename: Naoto
authors.initials: N
authors.lastname: Tatewaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishida
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Teruo
authors.initials: T
authors.lastname: Miyazawa
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology; D003373:Coumaric Acids / Q000494:pharmacology*; D015536:Down-Regulation; D004357:Drug Synergism; D006801:Humans; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003373:Coumaric Acids; D014810:Vitamin E; C082097:tocotrienol, delta; C004999:ferulic acid; C509186:TERT protein, human; D019098:Telomerase