PITTSBURGH, June 1 -- Scientists at the University of Pittsburgh have discovered how a novel form of vitamin K exerts its cancer-killing effects in primary liver cancers, which are notoriously resistant to chemotherapy. The research results, published in the May issue of The Journal of Biological Chemistry, describe an important new way to treat, and possibly prevent, cancer by triggering programmed cell death.
"Our finding is extremely important if we are to maximize the use of vitamin K compounds against cancer," noted Brian Carr, M.D., Ph.D., FRCP, professor of surgery in the Thomas E. Starzl Transplantation Institute and director of the Liver Cancer Center at the University of Pittsburgh Cancer Institute (UPCI). "Through our ongoing research, we now know that the vitamin K compounds not only can kill liver cancers, but also can destroy other types of cancer in tissue cultures, including breast cancer and melanoma. They do so by a quite novel growth-regulating mechanism."
"One of the attractive features of this unique compound is that it appears to stop cancer cell growth without producing toxicity. We now are testing this compound against cancers in rats, and given positive results, we hope to begin clinical trials of this agent within two years."
The Pitt research team found that a vitamin K analog, Compound 5 (Cpd
5), causes an imbalance in the normal activity of enzymes that control the
addition or removal of small molecules called phosphate groups from selected
proteins inside cells. Specifically, Cpd 5 blocks the activity of enzymes
called protein-tyrosine phosphatases, which normally remove phosphate groups
from selected proteins inside liver cancer cells. However, Cpd 5 does not
interfere with another group of enzymes called protein tyrosine-kinases, which
add phosphate groups to these same proteins. The result is an excess of what are called
tyrosine phosphorylated proteins, which trigger a variet
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Contact: Lauren Ward
wardla@a1.isd.upmc.edu
412-624-2607
University of Pittsburgh Medical Center
1-Jun-1998