December 14, 2004

Vitamin E in plant seeds could halt prostate, lung cancer, says Purdue scientist

WEST LAFAYETTE, Ind. – The form of vitamin E found in many plant seeds – but not in most manufactured nutritional supplements – might halt the growth of prostate and lung cancer cells, according to a Purdue University study.

A team led by Qing Jiang (pronounced "ching zhang") has found that gamma-tocopherol, which occurs naturally in walnuts, pecans, sesame seeds, and in corn and sesame oils, inhibits the proliferation of lab-cultured human prostate and lung cancer cells. The vitamin's presence interrupts the synthesis of certain fatty molecules called sphingolipids, important components of cell membranes. However, the gamma-tocopherol leaves healthy human prostate cells unaffected, which could give it value as an anticancer agent.

"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 Jiang, who is an assistant professor of foods and nutrition in the College of Consumer and Family Sciences. "This could be wonderful news for cancer patients if the effect can be reproduced in animal models. But because most nutritional supplements contain only alpha-tocopherol, a different form of vitamin E that alone does not have these anticancer properties, it may be better to supplement the diet with mixed forms of vitamin E. The study shows that the anticancer effect is enhanced when mixed forms are used."

Jiang's research appears in the current (week of Dec. 13) online edition of the scientific journal Proceedings of the National Academy of Sciences. She co-authored the paper with Jeffrey Wong, Henrik Fyrst, Julie D. Saba and Bruce N. Ames of the Children's Hospital Oakland Research Institute in Oakland, Calif.

Scientists have been studying vitamin E for more than three-quarters of a century, but most efforts have focused largely on alpha-tocopherol, one of eight known forms in the vitamin's family. Alpha-tocopherol was found early on to have the most beneficial effects on laboratory animals fed diets deficient in vitamin E, and also is the major form found in body tissues. For these reasons, it has been nearly the only form of the vitamin to be included in most manufactured nutritional supplements.

"Since then, alpha-tocopherol has justifiably earned a good reputation as an antioxidant, which helps to fight against damage caused by unwanted free radicals," Jiang said. "But its familiarity has perhaps attracted research away from the other seven forms of vitamin E, and since gamma-tocopherol is the vitamin's most commonly occurring natural form in the American diet, I grew interested in it a few years ago."

In 2000 another study by Jiang and colleagues found that gamma-tocopherol inhibits inflammation, which had already been implicated in cancer development. They theorized that it might retard the progress of cancer and cardiovascular disease, and to test their hypothesis they exposed cultures of cancerous prostate and lung cells to the vitamin. Normal prostate epithelial cells were used as a control group.

"We discovered that as we increased the quantity of gamma-tocopherol, the cancer cells grew more slowly," Jiang said. "But the normal prostate cells were not affected and grew normally. This could indicate that the vitamin could be used to target lung and prostate cancer cells without the damaging side effects of chemotherapy."

The study also revealed that gamma-tocopherol caused cell death by interrupting sphingolipid synthesis.

"This is also a novel discovery," Jiang said. "Although there have been prior indications that some form of vitamin E may cause cell death in some mouse cell lines, we are the first to provide a mechanism for such an effect."

Gamma-tocopherol, though rarely available in vitamin pills, is nevertheless found in abundance in the typical American diet. Many nuts are rich in it, including walnuts and pecans, as are cooking oils such as corn and sesame oil.

Though Jiang said she would be cautious about using food sources to slow prostate or lung cancer's progress in humans, she said that high-risk groups such as older men could benefit from supplementation – if carried out with prudence.

"Foods rich in gamma-tocopherol are also rich in fats, and some products bring other hazards as well," she said. "Corn oil, for example, is rich in linolic acid, which has been shown to promote certain types of cancer in some studies. But sesame seeds and pecans seem to be good all-around choices."

Jiang said the next step for her research team would be testing the effect of gamma-tocopherol and mixed forms of vitamin E on animal cancers.

"Although this discovery is promising, we do not yet know whether gamma-tocopherol has any effect on cancer in living creatures," she said. "We hope that future research not only will clarify whether gamma-tocopherol could have applications in human cancer treatment, but also will show how we might supplement the body with the vitamin to prevent cancer from developing in the first place. These questions will continue to direct our work."

This research was funded in part by the National Institutes of Health.

Writer: Chad Boutin, (765) 494-2081, cboutin@purdue.edu

Source: Qing Jiang, (765) 494-2483 or 496-6407, qjiang@purdue.edu

Purdue News Service: (765) 494-2096; purduenews@purdue.edu

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Online paper in Proceedings of the National Academy of Sciences

g -Tocopherol (g T), the predominant form of vitamin E in diets, but not a -tocopherol (a T), the major vitamin E form in tissues and supplements, inhibits proliferation of prostate (LNCaP, PC-3) and lung (A549) cancer cells. In contrast, at similar concentrations, g T had no effects on normal prostate epithelial cells. Combinations of some vitamin E forms such as g T and d -tocopherol (d T) exhibit additive or synergistic inhibitory effects. g T, and its combination with d T, induced apoptosis in androgen-sensitive prostate LNCaP, but not androgen resistant PC-3 cells, by the induction of cytochrome C release, activation of caspase 9 and caspase 3, cleavage of 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 g T-induced DNA fragmentation, cytochrome C release, PARP cleavage and the formation of active caspase 3. Compared with vehicle-treated controls, g T treatment led to pronounced dihydroceramide and dihydrosphingosine accumulation, which preceded morphological and biochemical manifestations of apoptosis. In contrast, ceramide levels did not increase until day 3, when substantial cell death took place. Our study demonstrates that g 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.

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