Effects of nitrosylcobalamin on NF-kB survival signaling and antitumor activity of Apo2L/TRAIL: Abstract No. 5580 Acting on the knowledge that many tumor cells crave the micronutrient cobalamin—more commonly known as vitamin B12—a team of cancer researchers from Cleveland has designed a modified B12 molecule that delivers a cellular toxin to kill tumor cells. The ‘Trojan Horse’ modification of the vitamin B12 molecule induces tumor cell mechanisms to cause cell death. Daniel Lindner, M.D., Ph.D. and Joseph Bauer, Ph.D. described how tumor cells have a desperate need for high amounts of vitamin B12, suggesting a new and devious method to deliver targeted drugs to the cancer. “Tumors crave Vitamin B12 because cancer cells have an imperative need for methionine in protein production,” Lindner said. “All cells need vitamin B12 to convert homocysteine to methionine, but cancer cells have a greater need.” To satisfy their cellular craving for the vitamin, tumor cells produce excessive amounts of the receptor that attaches to available blood-borne vitamin B12. The receptors import the vitamin inside of the cell membrane. Since tumor cells produce far more—ten times or more— the number of receptors for Vitamin B12 than normal cells, the concentrations of the vitamin build up within tumor cells. Taking advantage of tumor cell uptake of large quantities of vitamin B12, Bauer modified the vitamin to include nitric oxide. The new molecule, called nitrosylcobalamin, latches onto B12 receptors and delivers a knockout punch to the tumor cell. “Tumor cells hungrily ingest the modified Vitamin B12, just as they do the natural micronutrient,” Bauer said. Inside the tumor cell, however, the nitric oxide component of the targeted drug is released, triggering cellular events leading to up-regulation of genes causing apoptosis--or programmed cell death. Lindner and Bauer documented how the elevated levels of nitric oxide in the tumor cells inhibit a molecular pathway that normally promotes cell survival. By hampering the activity of the NFkB pathway, elevated nitric oxide promotes apoptosis in tumor cells. Nitrosylcobalamin also up-regulates the Apo2/TRAIL pathway directly leading to apoptosis. The novel technology is potent against tumor cells in culture, while relatively benign to normal cells. In animal models, the ‘Trojan Horse’ dramatically reduces tumor size. In combination with interferon treatment, which encourages further elevation of Vitamin B12 receptor levels in tumor cells, nitrosylcobalamin leads to complete tumor regression in mice. “In principle, this targeted therapeutic will be effective in human tumors,” Lindner said. “Testing will tell.” Lindner and his colleagues are members of the Taussig Cancer Center and the Department of Cancer Biology at the Cleveland Clinic. AACR, 2004 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.