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Gamma Tocopherol Form of Vitamin E Induces Cell Death in Human Prostate and Lung Cancer Cells

According to a study published in the December 2004 issue of the proceedings of the National Academy of Sciences, gamma-tocopherol inhibited the production of lab-cultured human prostate and lung cancer cells. Gamma tocopherol is the predominant form of Vitamin E in food, whereas Alpha tocopherol is the major form of Vitamin E in tissues and supplements.

Although the presence of gamma-tocopherol caused cell death by interrupting the synthesis of sphingolipids (certain fatty molecules, which are important components of cell membranes), it left healthy human prostate cells unaffected. As researchers increased the amount of gamma-tocopherol, cancer cells slowed in growth and healthy cells grew normally.

"This is the first time gamma-tocopherol has been shown to induce death in lab-grown human cancer cells while leaving healthy cells alone," said the head researcher of the study.

This study explains why prior studies using a combination of Vitamin E from food sources and supplements provided conflicting results.

Combining Forms of Vitamin E

Since gamma-tocopherol does not appear in most manufactured nutritional supplements, researchers have suggested combining it with another form of vitamin E: Alpha-tocopherol.

Alpha-tocopherol is the major form of vitamin E found in the body and, in contrast to gamma-tocopherol, is found in most manufactured nutritional supplements. It has justifiably earned a good reputation as an antioxidant, which helps fight against damage caused by unwanted free radicals. Thus, it is better to supplement a diet with mixed forms of vitamin E, as together they will enhance the positive effects found in each.

Maximum Vitality contains all the tocopherol and tocotrienol forms of Vitamin E.

For Medical Professionals

{gamma}Tocopherol ({gamma}T), the predominant form of vitamin E in diets, but not {alpha}-tocopherol, the major vitamin E form in tissues and supplements, inhibits proliferation of prostate cancer cells (LNCaP and PC-3) and lung cancer cells (A549). In contrast, at similar concentrations, {gamma}T has no effect on normal prostate epithelial cells. Combinations of some vitamin E forms, such as {gamma}T and {delta}-tocopherol, exhibit additive or synergistic inhibitory effects. In this study, {gamma}T or its combination with {delta}-tocopherol induced apoptosis in androgen-sensitive prostate LNCaP, but not in androgen-resistant PC-3 cells, by the induction of cytochrome c release, activation of caspase 9 and caspase 3, cleavage of poly-ADP-ribose polymerase (PARP), and involvement of caspase-independent pathways. Myriocin and fumonisin B1, specific inhibitors of key enzymes (serine palmitoyltransferase and dihydroceramide synthase, respectively) in de novo synthesis of sphingolipids, significantly protected cells from {gamma}T-induced DNA fragmentation, cytochrome c release, PARP cleavage, and the formation of active caspase 3. Compared with vehicle-treated controls, {gamma}T treatment led to pronounced dihydroceramide and dihydrosphingosine accumulation, which preceded morphological and biochemical manifestations of apoptosis. In contrast, ceramide and shpingosine levels did not increase until day 3, when substantial cell death took place. Our study demonstrates that {gamma}T and mixed vitamin E forms induce cell death by interrupting the de novo sphingolipid pathway in a prostate cancer cell line. Thus, certain vitamin E forms may be valuable as anticancer agents.


Proceedings of the National Academy of Sciences December 21, 2004;101(51):17825-17830

Qing Jiang *, Jeffrey Wong *, Henrik Fyrst *, Julie D. Saba * and Bruce N. Ames *,
*Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609; and Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720

Key concepts: Vitamin E, gamma tocopherol, prostate cancer, sphingolipids