Chemoprevention of Azoxymethane-Induced Colon Carcinogenesis by Delta-Tocotrienol

Menée in vitro, in vivo et à l'aide d'un modèle murin de carcinogenèse colorectale, cette étude analyse le rôle du delta-tocotriénol (DT3), une forme bioactive de la vitamine E, dans l'inhibition de la croissance tumorale

Résumé en anglais

This study evaluated the preclinical activity of δ-tocotrienol (DT3), a bioactive form of vitamin E, in the inhibition of colorectal cancer growth and development in vitro and in vivo. DT3 is the most bioactive isomer of vitamin E in inhibiting growth of colorectal cancer cells. However, it had little effect on the proliferation of normal colon mucosal cells NCM460. In HCT-116 and SW-620 colorectal cancer cells, DT3 (50 µM) significantly inhibited malignant transformation (P < .02, P < .001), cell migration (P < .02, P <.05) and invasion (P < .05, P < .01) compared to vehicle. DT3 inhibited markers for epithelial (E-cadherin) to mesenchymal (vimentin) transition, metastasis (matrix metalloproteinase 9), angiogenesis vascular endothelial growth factor (VEGF), inflammation (NF-kB), and Wnt signaling (β-catenin) compared to vehicle in colorectal cancer cells. DT3 induced apoptosis selectively in colorectal cancer cells (SW-620 cells, HCT-116 cells, and HT-29) without affecting the normal colon cells. In the Azoxymethane-induced colorectal carcinogenesis model in rats, DT3 (200 mg/kg orally twice a day) for 20 weeks significantly inhibited colorectal polyps by 70% and colorectal cancer by almost 99% compared to the vehicle treatment group (P < .02, P < .001), and the cancer inhibition effect was more potent than sulindac (50%). Taken together, these data demonstrate that DT3 is a potential chemopreventive agent in colorectal cancer, warranting further investigation into its clinical use in the prevention and treatment of colorectal cancer.