Research Shows the Role of Vitamin A in Fighting Cancer

According to a report from the University of Maryland, Baltimore (UMB), a compound, VN/14-1, that stops retinoic acid, which is derived from vitamin A, from breaking down, is also effective in treating animal models of human prostate cancer.

They found that by giving daily injections of VN/14-1, they were able to achieve an up to a 50% decrease in the volume of tumors in mice that had been implanted with human prostate cancer cells

The most important fact is that VN/14-1acted in many different ways. It causes cancer cells to differentiate by making them revert back to its non cancerous state and it also stops the growth of the cancer by stopping the cell cycle and induces the cells to die by programing the cell death.

When the body converts vitamin A into retinoic acid, it becomes involved in the maintenance of normal cell growth and other studies have shown that prostate cancer cells have anywhere from 5 to 8 times less retinoic acid than is found in non cancerous prostate cells. The researchers have been able to develop several compounds, of which VN/14-1is just one, with the aim being to inhibit the normal breakdown of the retinoic acid that occurs in cancer cells.

The agent functions much like Retin-A, which is used for treating acne as well as an anti aging therapy and also like the leukemia drug Vesanoid.

These are called retinoida and they add all-trans retinoic acid (ATRA) to either the skin or cancer cells. VN/14-1is a retinoic acid metabolism blocking agent (RAMBA) that works by inhibiting the breakdown of ATRA, which keeps more of the retinoic acid in the cancer cells and that enables the retinoic acid to be able to redirect the cancer cells back into their normal growth patterns and that process includes programmed cancer cell death.

The concept is that instead of giving extra ATRA it would be better to stop the ATRA already in the cells from breaking down.

VN/14-1 actually works by blocking the CYP26 enzyme, which is the compound that actually changes the ATRA into inactive compounds. They have been tested VN/14-1 in breast cancer cells and have received further funding for the study of VN/14-1 in pre clinical trials and if these are successful, the next step will be a Phase I human clinical trial.

In this one study they used mouse models of human prostate cancer and found that when the mice were injected with a 5 milligram per kilogram daily dose of VN/14-1, there was a 33% reduction in the size of the tumor and when they doubled the dose it went up to 50%

They also tried a dose of 20 mg/kg administered by oral and intravenous methods in order to study the concentration of the compound in the blood of rats over a period of time.
After VN/14-1 was administered orally, the amount that was in the blood was exceptionally high when compared to the amount from the intravenous method. This shows that further testing of VN/14-1 should be done orally, since this is the method that is much preferred in humans.

The lead researcher is Vincent C.O. Njar, Ph.D. who is an associate professor in the Department of Pharmacology and Experimental Therapeutics within UMB's School of Medicine.

Grants for the study came from the National Institutes of Health and National Cancer Institute, the U.S. Department of Defense, and UMB's Marlene and Stewart Greenebaum Cancer Center

Source: American Association for Cancer Research (AACR) http://newswise.com/