Vitamin A Studied as Possible Preventive Agent Against Cancer

NCI CAM Annual Report-FY10

Vitamin A is an essential nutrient that plays a crucial role in a wide range of biological processes, from bone growth and vision to immune function and cellular maturation. Compounds derived from vitamin A have been used to treat cancer with mixed results. The vitamin’s role in cancer appears to be complex: recent evidence suggests that, in certain cir­cumstances, it may inhibit cancer in some, but promote cancer in others. Nevertheless, a large body of scientific literature supports the role of vitamin A in blocking the proliferation and maturation of breast cancer cells. Unfortunately, the doses required to achieve these effects pro­duce adverse side effects and therefore cannot be used for cancer prevention.

An alternative and potentially less toxic ap­proach might be to find a way to deliver imma­ture forms (or precursors) of vitamin A to breast cells and make use of the cells’ own machinery to turn the precursors into retinoic acid (the active form of vitamin A), explains Matthew J. Rowling, Ph.D., of Iowa State University, who is being funded by NCI* to determine how to optimally use vitamin A for breast cancer prevention.

Because the mechanisms by which vitamin A enters breast cells are poorly understood, it has not been clear how to deliver the vitamin A precursors into the cells. Dr. Rowling’s research initially focused on a group of cell-membrane proteins that are found in breast cells and had previously been shown to be essential in enabling both vitamin D and retinol (the main circulating form of vitamin A) to gain entry into kidney cells. A series of experiments, however, failed to show that these proteins were actively involved in helping retinol gain entry to breast cells. Then scientists at the University of California Los Angeles (UCLA) published a paper** in which they identified a receptor, dubbed STRA6, that separates retinol from its binding protein and ushers it inside cells, where it is then broken down. These experiments were conducted in cells from the retina (the mem­brane at the rear of the eyeball that is important for vision), raising the question as to whether STRA6 also facilitates retinol uptake in other types of cells.

Dr. Rowling turned his attention to trying to elucidate whether STRA6 is the mechanism by which vitamin A enters cancer cells or cells susceptible to cancer. His experiments to date seem to confirm that the mechanism described by the UCLA scientists is at work not only in breast cells but also in colon and prostate cells.

“Our thinking now is that STRA6 is essential for the uptake and anti-proliferative effects of vitamin A in breast, colon, and prostate cells,” he said. “A corollary to this is that if STRA6 is missing or disabled, vitamin A–mediated control of cell proliferation might be lost, creating the conditions for a cancer to develop. A deficiency of STRA6 could be a marker for increased risk for breast, colon, or prostate cancer.”

If follow-up studies confirm this hypothesis, Dr. Rowling’s research could lead to novel approaches to cancer prevention by boosting vitamin A uptake in these organs.