The cancer-preventive activity of vitamin E has been studied. Whereas some epidemiological studies have suggested a protective effect of vitamin E against cancer formation, many large-scale intervention studies with alpha-tocopherol (usually large doses) have not demonstrated a cancer-preventive effect. Studies on alpha-tocopherol in animal models also have not demonstrated robust cancer prevention effects. One possible explanation for the lack of demonstrable cancer-preventive effects is that high doses of alpha-tocopherol decrease the blood and tissue levels of delta-tocopherols. It has been suggested that gamma-tocopherol, due to its strong anti-inflammatory and other activities, may be the more effective form of vitamin E in cancer prevention. Our recent results have demonstrated that a gamma-tocopherol-rich mixture of tocopherols inhibits colon, prostate, mammary and lung tumorigenesis in animal models, suggesting that this mixture may have a high potential for applications in the prevention of human cancer. In this review, we discuss biochemical properties of tocopherols, results of possible cancer-preventive effects in humans and animal models and possible mechanisms involved in the inhibition of carcinogenesis. Based on this information, we propose that a gamma-tocopherol-rich mixture of tocopherols is a very promising cancer-preventive agent and warrants extensive future research.

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Previously it was shown that combined low dose treatment of tocotrienols and statins synergistically inhibited the growth of highly malignant +SA mammary epithelial cells in culture. Therefore, the objective of the present work was to prepare and characterize lipid nanoparticles that combined simvastatin and tocotrienol rich fraction (TRF) as potential anticancer therapy. The entrapment of simvastatin in the oily nanocompartments, which were formed by TRF inclusion into the solid matrix of the nanoparticles, was verified by its high entrapment efficiency and the absence of endothermic or crystalline peaks when blends were analyzed by DSC and PXRD, respectively. The release of simvastatin from the nanoparticles in sink conditions was characterized by an initial burst release of approximately 20% in 10h followed by a plateau. No significant change in particle size (approximately 100 nm) was observed after storage for six months. The anticancer activity of the nanoparticles was verified in vitro by observing their antiproliferative effects on malignant +SA mammary epithelial cells. The IC(50) of the reference alpha-tocopherol nanoparticles was 17.7 microM whereas the IC(50) of the simvastatin/TRF nanoparticles was 0.52 microM, which confirmed the potency of the combined treatment and its potential in cancer therapy.

The present study investigated the effects of a preparation of a g-tocopherol-rich mixture of tocopherols (g-TmT) on chemically induced lung tumorigenesis in female A/J mice and the growth of H1299 human lung cancer cell xenograft tumors. In the A/J mouse model, the lung tumors were induced by either 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK; intraperitoneal injections with 100 and 75 mg/kg on Week 1 and 2, respectively) or NNK plus benzo[a]pyrene (B[a]P) (8 weekly gavages of 2 mmole each from Week 1 to 8). The NNK plus B[a]P treatment induced 21 tumors per lung on Week 19; dietary 0.3% g-TmT treatment during the entire experimental period significantly lowered tumor multiplicity, tumor volume and tumor burden (by 30, 50 and 55%, respectively; P < 0.05). For three groups of mice treated with NNK alone, the g-TmT diet was given during the initiation stage (Week 0 to 3), post-initiation stage (Week 3 to 19) or the entire experimental period, and the tumor multiplicity was reduced by 17.8, 19.7 or 29.3%, respectively (P < 0.05). g-TmT treatment during the tumor initiation stage or throughout the entire period of the experiment also significantly reduced tumor burden (by 36 or 43%, respectively). In the xenograft tumor model of human lung cancer H1299 cells in NCr-nu/nu mice, 0.3% dietary g-TmT treatment significantly reduced tumor volume and tumor weight by 56 and 47%, respectively (P < 0.05). In both the carcinogenesis and tumor growth models, the inhibitory action of g-TmT was associated with enhanced apoptosis and lowered levels of 8-hydroxydeoxyguanine, g-H2AX and nitrotyrosine in the tumors of the g-TmT-treated mice. In cell culture, the growth of H1299 cells was inhibited by tocopherols with their effectiveness following the order of d-T > g-TmT > g-T, whereas a-T was not effective. These results demonstrate the inhibitory effect of g-TmT against lung tumorigenesis and the growth of xenograft tumors of human lung cancer cells. The inhibitory activity may be due mainly to the actions of d-T and g-T.