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 apoptosis.
"Our finding is extremely important if we are to maximize the
use of vitamin K compounds against cancer," noted Brian Carr,
MD, PhD, 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 2 years."
The 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 protein-tyrosine phosphatases, which normally remove
phosphate groups from selected proteins inside liver cancer cells.
Compoun 5 does not, however, interfere with protein tyrosine-kinases,
which add phosphate groups to these same proteins. The result is an
excess of tyrosine-phosphorylated proteins, which trigger a variety
of activities within cells. They exert anticancer effects by inducing apoptosis.
Liver cancer is thought to be one of the three most common cancers
worldwide. The disease caused about 13,000 deaths in the United
States in 1998 alone. Major causes of this cancer include infection
with either hepatitis B or C or chronic alcohol consumption. In the
United States and other developed countries, liver cancer may be
treated by resection or transplantation. Liver transplantation is
costly, however, and often unavailable due either to the scarcity of
donated organs or the advanced nature of the cancer at diagnosis.
"By providing this modified vitamin K to individuals at known
risk of developing liver cancer, we might be able to reduce the
incidence of this devastating illness. By treating liver cancer with
this agent, we possibly could remove some individuals with this
disease from transplant waiting lists, if it is as effective in
humans as it is experimentally," said Dr. Carr.
Dr. Carr and his colleagues recently reported that Cpd 5 can inhibit
liver regeneration in rats that had part of their livers removed. The
animals suffered no toxic side effects.
The new vitamin K is not in clinical testing at present. For more
information about ongoing clinical trials, patients and physicians
can, however, contact the UPCIs Cancer Information and Referral
Service by calling 1(800) 237-4PCI (4724) or (412) 624-1115 or by
visiting UPCIs web site at http://www.upci.upinc.edu.