February 4, 1997
University of Illinois at Chicago Office of Public Affairs
Contact:
Jody Oesterreicher 312/996-8277 or [email protected]
Embargoed for release at 4 p.m. EST Feb. 4, 1997
University of Illinois at Chicago researchers have synthesized a new vitamin D-5 compound that may prevent cancer without the toxicity associated with most vitamin D-3 compounds.
The natural metabolite of vitamin D-3, which effectively inhibits cancer cell growth in laboratory animals, increases calcemic activity, the amount of potentially toxic calcium circulating in the body. If calcemic activity is high, toxicity can be fatal.
Researchers around the world have synthesized more than 1,200 vitamin D-3 compounds, leaving vitamins D-4, D-5 and D-6 largely unexplored until UIC investigators undertook their study. The UIC unit's findings will be published Feb. 5 in the Journal of the National Cancer Institute.
The UIC researchers compared the activity of their newly synthesized vitamin D-5 compound to a biologically active natural form of vitamin D-3. They tested both compounds' calcemic activity at various doses on vitamin D-deficient rats. The vitamin D-3 compound was four times more calcemic than the vitamin D-5 compound.
The researchers then tested the effectiveness of both compounds against the development of precancerous lesions, using mouse mammary glands exposed to a common carcinogen. Both compounds inhibited lesions as much as 100 percent at the highest concentrations. Though the vitamin D-3 compound shows activity against cancer cells at lower concentrations than the vitamin D-5 compound, it also is toxic. The vitamin D-5 compound, on the other hand, is nontoxic at active concentrations.
Lastly, the UIC team tested the effect of the compounds on the expression of vitamin D receptors and transforming growth factor. Vitamin D receptors are proteins to which vitamin D binds. The presence of vitamin D receptors is linked to both the inhibition of cell growth and increased differentiation of cancer cells. When cells differentiate they assume normal cellular function. Transforming growth factor is a polypeptide secreted by cells and its presence is linked to inhibition of cancer cell growth. Exposure of normal mouse mammary glands and human breast cancer cells to both vitamin compounds dramatically induced the expression of the receptors and growth factor.
"Induction of transforming growth factor has always been shown in cancer cells, but this is the first time it has been shown to be induced in normal cells," said Rajendra Mehta, project leader of the study and professor of surgical oncology at UIC.
Mehta and his colleagues already are testing the newly synthesized vitamin D-5 compound on mice carrying human cancer cells, studying the molecular mechanism of vitamin D-5 to aid in the generation of new compounds and synthesizing new vitamin D-5 and D-6 compounds.
"This work is opening up research to a whole new class of vitamin D compounds. When you start with a non-toxic compound like the one we synthesized you always can do better," Mehta said.
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