δ-Tocotrienol suppresses tumorigenesis by inducing apoptosis and blocking the COX-2/PGE2 pathway that stimulates tumor–stromal interactions in colon cancer

• Main Authors: S. Wada, Y. Naito, Y. Matsushita, M. Nouchi, M. Kawai, E. Minami, W. Aoi, S. Ikeda, A. Higashi, T. Yoshikawa
• Format: Article
• Language: English
• Published: Elsevier 2017-08-01
• Series: Journal of Functional Foods
• Subjects: Colon adenocarcinoma; Colorectal cancer; δ-Tocotrienol; Vitamin E; Stromal cells
• Online Access: http://www.sciencedirect.com/science/article/pii/S1756464617303183

Anticancer effects of δ-tocotrienol have been reported for several types of cancer, but have not been fully elucidated in colorectal cancer. We investigated the anti-proliferative effect of tocotrienols in vitro, in colon epithelial cells and stromal cells, and in vivo, in an induced colorectal cancer mouse model. Of the four isoforms tested, δ-tocotrienol exerted the most potent anti-proliferative effect on colon adenocarcinoma cells. δ-Tocotrienol reduced the nitrite and prostaglandin E2 (PGE2) concentrations in mouse embryonic fibroblasts (MEFs) pretreated with δ-tocotrienol and stimulated with lipopolysaccharide (LPS) and interferon γ. Furthermore, supernatants of LPS-stimulated MEFs promoted adenocarcinoma cell proliferation, while δ-tocotrienol treatment suppressed this effect. Additionally, a δ-tocotrienol-enriched diet significantly suppressed tumor formation in azoxymethane and dextran sulfate sodium-treated mice. Taken together, these data suggest that a δ-tocotrienol-enriched diet prevents colorectal cancer. At the molecular level, tocotrienols exert a direct anti-proliferative effect on colon adenocarcinoma cells, and an indirect, stromal cell-mediated, anti-proliferative effect.