The scientists manipulated the structure of that vitamin E molecule and found that the effectiveness of this new agent they created was 20-fold higher than the vitamin itself in cells. In experiments in mice, this agent reduced the size of prostate cancer tumors.
These findings suggest that an agent based on the chemical structure of one form of vitamin E could help prevent and treat numerous types of cancer particularly those associated with a mutation in the PTEN gene, a fairly common cancer-related genetic defect that keeps Akt active.
The researchers began the work with both alpha and gamma forms of the vitamin E molecule. Both inhibited the enzyme called Akt in very targeted ways, but the gamma structure emerged as the more powerful form of the vitamin.
In effect, the vitamin halted Akt activation by attracting Akt and another protein, called PHLPP1, to the same region of a cell where the vitamin was absorbed: the fat-rich cell membrane. PHLPP1, a tumor suppressor, then launched a chemical reaction that inactivated Akt, rendering it unable to keep cancer cells alive.
"This is a new finding. We have been taking vitamin E for years but nobody really knew about this particular anti-cancer mechanism," Chen said.
The gamma form was most effective because its chemical shape allowed it to attach to Akt in the most precise way to shut off the enzyme.
Because of how the various molecules interacted on the cell membrane, the scientists predicted that shortening a string of chemical groups dangling from the main body, or head group, of the gamma-tocopherol molecule would make those relationships even stronger. They lopped off about 60 percent of this side chain and tested the effects of the new agent in the prostate cancer cells.
"By reducing two-thirds of the chain, the molecule had a 20 times more potent anti-tumor effect, while retaining the integrity of vit
|Contact: Ching-Shih Chen|
Ohio State University