Abstract
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 μmol/L) significantly inhibited malignant transformation (P < 0.02, P < 0.001), cell migration (P < 0.02, P < 0.05), and invasion (P < 0.05, P < 0.01) compared with vehicle. DT3 inhibited markers for epithelial (E-cadherin) to mesenchymal (vimentin) transition, metastasis (matrix metalloproteinase 9), angiogenesis VEGF, inflammation (NF-κB), and Wnt signaling (β-catenin) compared with 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 with the vehicle treatment group (P < 0.02, P < 0.001), 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.
Highlights
Colorectal cancer is the third most commonly diagnosed cancer worldwide with over 1 million new cases annually, often found in people ages 50 or older, with a median age at diagnosis of 70 years [1, 2]
Effects of different forms of tocopherols and tocotrienols on colon cancer cell growth We first analyzed the concentration-dependent response of tocopherols (AT, BT, GT, and DT) and tocotrienols (AT3, BT3, GT3, and DT3-treated group (DT3)) on cell proliferation by MTT assay in colon cancer cells (HCT-116)
Data show that BT3, GT3, and DT3 significantly inhibited the cell proliferation of HCT-116 cells, but AT3 and tocopherols (AT, BT, GT, and DT) had little effect on colon cancer cell growth (Fig. 1A)
Summary
Colorectal cancer is the third most commonly diagnosed cancer worldwide with over 1 million new cases annually, often found in people ages 50 or older, with a median age at diagnosis of 70 years [1, 2]. It is one of the most common causes of cancer-related deaths at over half a million annually [1, 3]. The most commonly investigated chemopreventive agents are nonsteroidal anti-inflammatory drugs. They have been shown to reduce the incidence of colorectal cancer when used long-term. Novel and safe chemopreventive agents are urgently needed for patients with colorectal cancer
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