A chemically altered form of vitamin E mixed into mouse chow dramatically reduced spread of aggressive mammary cancer in mice, suggesting that the compound in pill form could be used to treat human metastatic cancer, according to a report in the October 1 issue of the journal Cancer Research.
The study, by investigators at the University of Arizona, is the first to show that the synthetic compound has potent anti-cancer properties when given in the simplest way possible − as a dietary supplement.
"We tried other ways of delivering different forms of the synthetic vitamin, such as by force feeding and injections, but found that one form, alpha-TEA, was more effective when incorporated into food, and that makes it much more clinically useful," said the study's lead investigator, Emmanuel T. Akporiaye, Ph.D., professor in the Department of Immunobiology at the University of Arizona.
Mice eating the super chow had a 4.8-fold reduction in the number of tumors that spread to the lungs, compared to control mice, Akporiaye said. An even greater effect was seen when the animals began eating alpha-TEA-laced food as a cancer preventive, he said.
"These preliminary studies are very promising, and it could be that combining this synthetic vitamin E derivative with other anti-cancer treatments may offer the potential of both treating and preventing human breast cancer," Akporiaye said.
Although vitamin E (alpha tocopherol) is an anti-oxidant, it cannot destroy tumor cells by itself, he said. To improve the vitamin, derivatives have been created by swapping a hydroxyl chemical group with an acid. One is alpha-tocopheryl succinate (alpha-TOS), which used a succinic acid residue, and another is alpha-tocopheryloxyacetic acid (alpha-TEA), which used acetic acid.
Replacing the hydroxyl group in vitamin E helps force cancer cells to self destruct, Akporiaye said, because the compounds work to free up pro-apoptotic proteins that are normally held in check within cells. "Cell survival is maintained when pro-apoptotic proteins are confined, and these synthetic forms of vitamin E release them, pushing the cell into committing suicide," he said.
"Only a little part of vitamin E is changed in these synthetic derivatives, but they show amazing anticancer properties, and they selectively target tumor cells," Akporiaye said.
To make the synthetic vitamins water soluble (not fat soluble like natural vitamin E), researchers have added sodium hydroxide. In this way, these vesiculated forms, called Valpha-TOS and Valpha-TEA, can be delivered clinically through injection or oral gavage (feeding through a tube), and experiments have shown they can treat melanoma, lung and breast cancer in rodent models.
In this study, the Arizona researchers evaluated the anti-tumor effect of Valpha-TOS and Valpha-TEA on mice with an aggressive form of mammary cancer that is similar to human breast cancer that readily metastasizes. They also looked at how well alpha-TEA would affect tumor growth if incorporated into the food ("chow") that the mice ate.
They found that injecting Valpha-TOS or Valpha-TEA into the peritoneal cavity of the mice reduced the average volume of tumors by two fold, compared to control mice that did not receive the injections. Administering Valpha-TOS daily through a feeding tube had the same effect on tumor size, but Valpha-TOS was ineffective when delivered in this way, Akporiaye said. "We found that Valpha-TOS wasn't stable, and returned to its natural vitamin E state," he said.