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  (Source: Futurity)
Study suggests special Vitamin E-derived drug will be most effective

Vitamin E is a vitamin used by the human body for a variety of purposes.  Composed of two groups of fused aromatic rings and a fatty tail, the vitamin commonly occurs in two varieties -- beta and gamma-Tocopherols.  Now a new study by Ohio State University suggests that vitamin E -- or synthetic analogues -- may be useful in fighting a broad spectrum of cancers.

I. Vitamin E Variants Can Fight Cancer

The new study by Ching-Shih Chen, professor of medicinal chemistry and pharmacognosy at The Ohio State University and an investigator in Ohio State’s Comprehensive Cancer Center, first examined Vitamin E's role in suppressing Akt, an enzyme that helps keep cancer cells alive.

Professor Chen comments, "This is the first demonstration of a unique mechanism of how vitamin E can have some benefit in terms of cancer prevention and treatment."

Akt is associated with keeping a variety of cancer cells alive.  It is common in many common cancerous cell types with PTEN gene mutations -- such as prostate cancers.  The excess Akt suppress apoptosis (cell death) granting the dangerous cells immortality.  But suppressing Akt allows the body's natural processes to trigger death of the tumor cells.

Before you rush to load up on Vitamin E pills beware -- the pills contain mostly alpha and beta-Tocopherols, forms of Vitamin E, which the study found to be less effective in suppressing Akt.  By contrast, the gamma form is generally poorly absorbed from dietary supplements and scarcer in pill formulations.
Vitamin E structure
γ Vitamin E and its derivatives are most effective in fighting cancer.
[Image Source: Wikimedia Commons]

Researchers discovered that by tweaking the structure of the more effective gamma variant -- shortening the fatty acid side chain -- they could get an even more impressive 20-fold increase in Akt suppression.

II. Mechanism of Action Identified, OSU Patents Drug

The researchers explain that the effect occurs when Vitamin E binds to Akt and sequesters it to the fatty lipid bilayer on the cell's inner surface.  The complex then attracts PHLPP1, an anti-tumor agent that binds and inactivates Akt.  Professor Chen explains, "This is a new finding. We have been taking vitamin E for years but nobody really knew about this particular anti-cancer mechanism.  By reducing two-thirds of the chain, the molecule had a 20 times more potent anti-tumor effect, while retaining the integrity of vitamin E’s head group."

Rodents injected with the Vitamin E-like chemical saw death of prostate cancer tumors, saving their lives.  At the same time the agent showed no toxicity or other adverse effects.
AKT1AKT2
AKT1 (left) and AKT2 (right) are common cancer-causing proteins, which the Vitamin E derivatives block. [Image Source: Wikimedia Commons]

While dietary vitamin E is crucial for other purposes, the successful tumor-killing properties of the vitamin E derivative could lead to a new non-toxic cancer therapy via either injections of the drug or ingested absorption.  Describes Professor Chen, "Our goal is to develop a safe pill at the right dose that people could take every day for cancer prevention. It takes time to optimize the formulation and the dose."

Ohio State has patented the Vitamin-E derived chemical, indicating that it hopes to commercialize it as a cancer treatment.

The work was funded by government grants from the National Institutes of Health, and a paper on the work was published in this month's issue of the peer-reviewed journal Science Signaling.

Sources: Ohio State Univ., Science Signaling



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Tocopherol, Akt inhibitors, etc
By jimhsu on 3/27/2013 2:55:39 PM , Rating: 2
Akt inhibitors are really nothing new; I use triciribine in the lab frequently, and it does a good job with specific inhibition. However, some of the properties of the non-alpha tocopherols and tocotrienols are more interesting than simply Akt inhibition; specifically, gamma tocopherols such as the ones mentioned in the article have much more anti-inflammatory activity than alpha-tocopherols, and are especially efficient scavengers of reactive nitrogen oxide species (RNOS). Here's a brief list of references from my database:

[23] Cooney, R. V.; Franke, A. A.; Harwood, P. J.; Hatch-Pigott, V.; Custer,
L. J.; Mordan, L. J. Gamma-tocopherol detoxification of nitrogen
dioxide: superiority to alpha-tocopherol. Proc. Natl. Acad. Sci. USA
90:1771–1775; 1993.

[24] Christen, S.; Woodall, A. A.; Shigenaga, M. K.; Southwell-Keely, P. T.;
Duncan, M. W.; Ames, B. N. gamma-tocopherol traps mutagenic
electrophiles such as NO(X) and complements alpha-tocopherol: physio-
logical implications. Proc. Natl. Acad. Sci. USA 94:3217–3222; 1997.

[25] Jiang, Q.; Christen, S.; Shigenaga, M. K.; Ames, B. N. gamma-tocopherol,
the major form of vitamin E in the US diet, deserves more attention. Am. J.
Clin. Nutr. 74:714–722; 2001.

[26] Wolf, G. gamma-Tocopherol: an efficient protector of lipids against nitric
oxide-initiated peroxidative damage. Nutr. Rev. 55:376–378; 1997.

[27] Wagner, K. H.; Kamal-Eldin, A.; Elmadfa, I. Gamma-tocopherol—an
underestimated vitamin? Ann. Nutr. Metab. 48:169–188; 2004.

[28] Jiang, Q.; Elson-Schwab, I.; Courtemanche, C.; Ames, B. N. gamma-
tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit
cyclooxygenase activity in macrophages and epithelial cells. Proc. Natl.
Acad. Sci. USA 97:11494–11499; 2000.

Before you go buy it though, know that although studies have demonstrated the difference between dietary (which contains gamma) and supplement (alpha) tocopherols, no controlled study has specifically looked at gamma supplementation.




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