At the right dose, vitamin D is important for bone development and may help protect against the development of several cancers, particularly colorectal cancer. However, large quantities designed to exploit the vitamin’s anticancer properties can lead to a toxic overdose of calcium in the blood. Now, research done at Georgetown University’s Lombardi Comprehensive Cancer Center indicates that it may be possible to separate the anticancer properties of vitamin D from its other functions.
Their study, reported in the journal Molecular Cell, found that mutant forms of the protein that binds to vitamin D in the cell do not allow vitamin D to promote bone development and calcium transport but do permit it to regulate an oncogenic protein known as beta catenin. Some modified forms of vitamin D itself, which do not alter bone and calcium, were also found to regulate beta-catenin.
“We found that we might be able to separate the two functions at the molecular level, and this raises the possibility that vitamin D can be chemically modified into a drug that will only have anticancer effects,” said Professor Stephen Byers, Ph.D. He and Salimuddin Shah, Ph.D., led an international group of investigators in this study.
The human body produces a lot of vitamin D from a brief exposure of the sun. The vitamin is made in the skin when a cholesterol-like molecule interacts with ultraviolet light. It has long been known that a lack of vitamin D can lead to the bone deformities associated with rickets, and the vitamin helps maintain calcium and phosphorous levels in bone and blood. Too much vitamin D, however, can spill calcium into the blood and lead to heart disease and death.
Population studies have also uncovered an interesting fact — that the risk of developing colon cancer is lower in people who live in sunny climates. Epidemiology studies have indicated that vitamin D is responsible for the protective effect of sunlight exposure on the incidence of several other cancers besides colon, including breast and prostate.
Byers and the research team suspected that beta catenin may interact with vitamin D in some fashion because of another known fact — activation of beta catenin causes most colon cancers.
To help them understand what vitamin D is doing in the cell, the researchers studied findings by other scientists who had looked at families who develop rickets due to an inherited mutation in their vitamin D receptor. Most of these patients had both rickets and alopecia (baldness). However a small number of families had mutations in the receptor which only led to rickets. “We know beta catenin is also involved in regulation of hair growth and we wondered if these particular mutations might also allow the receptor to regulate beta catenin,” Byers said.
“We found a mutation which caused rickets but not alopecia but which still allowed beta catenin to bind to the vitamin D receptor,” he said. This suggested to the researchers that it may be possible to separate the anti-cancer role of vitamin D from its effects on bone and calcium.
If a drug mimic of vitamin D can be developed, it could prove useful in preventing some cancers at their earliest stages, but would probably not offer any therapeutic benefit for later stage cancers, Byers said. “That’s because we know that by the time colon cancer is well advanced it fails to respond to vitamin D.”
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