| ironjustice@aol.com 2006-04-22, 11:22 am |
| Public release date: 20-Apr-2006
Contact: Nicole Kresge
nkresge@asbmb.org
301-634-7415
American Society for Biochemistry and Molecular Biology
Inhibition of iron-metabolizing enzyme reduces tumor growth
Bethesda, MD - A report in the Journal of Biological Chemistry shows
that inhibition of heme oxygenase-1, an enzyme involved in iron
metabolism, reduces Kaposi sarcoma tumor growth. This discovery could
result in the production of new drugs to treat this and other viral
cancers.
This research appears as the "Paper of the Week" in the April 21 issue
of the Journal of Biological Chemistry, an American Society for
Biochemistry and Molecular Biology journal.
Kaposi sarcoma is the most frequent tumor in AIDS patients and is
caused by infection of the patients with the Kaposi sarcoma-associated
herpes virus. The Kaposi sarcoma virus genome contains sequence that
encodes for a protein called viral G protein-coupled receptor (vGPCR)
that plays a key role in the development of tumoral lesions.
Interestingly, a study done in early 2004 showed that the cellular
production of a protein called heme oxygenase-1 could be turned on by
the Kaposi's sarcoma-associated herpesvirus. Heme oxygenase-1 is an
enzyme that is expressed in spleen and liver and is responsible for
breaking down heme, a molecule that consists of an iron atom surrounded
by a large ring of other atoms. Further evidence of the connection
between heme oxygenase-1 and the Kaposi's sarcoma virus came when
elevated levels of the protein were detected in biopsy tissue from oral
AIDS-Kaposi's sarcoma lesions.
"Taking into account the predominant function of vGPCR in Kaposi's
sarcoma and the elevated expression of heme oxygenase-1 observed in
Kaposi's sarcoma lesions, we decided to study whether vGPCR could
increase heme oxygenase-1 expression and if so, to explore the putative
role of the enzyme in vGPCR-dependent transformation," explains study
author Maria Julia Marinissen of the Universidad Autonoma de Madrid.
Marinissen and her colleagues found that vGPCR does indeed increase
production of the heme oxygenase-1 protein and the RNA that codes for
it. They also discovered that mice with tumors that were given specific
pharmacological inhibitors that blocked heme oxygenase-1 activity
showed a significant reduction in tumor growth without apparent side
effects.
"Considering that heme oxygenase-1 is overexpressed in human Kaposi's
sarcoma lesions, the inhibition of intratumoral heme oxygenase-1
activity by currently available drugs can represent a new anticancer
tactic in the treatment of Kaposi's sarcoma and may be of potential
clinical interest after more extensive investigation," says Marinissen.
"The inhibitor that we used in this study is a tin-protoporphyrin. A
recent clinical trial showed that the inhibitor can be administered to
newborns at any time point in the progression of postnatal
hyperbilirubinemia to rapidly and predictably block heme degradation
and prevent severe jaundice without significant short- or long-term
side effects. This is very important because it shows that the
inhibitor has been successfully used in human clinical trials to treat
diseases in which heme oxygenase-1 is involved."
###
The Journal of Biological Chemistry's Papers of the Week is an online
feature that highlights the top one percent of papers received by the
journal. Brief summaries of the papers and explanations of why they
were selected for this honor can be accessed directly from the home
page of the Journal of Biological Chemistry online at www.jbc.org.
The American Society for Biochemistry and Molecular Biology (ASBMB) is
a nonprofit scientific and educational organization with over 11,000
members in the United States and internationally. Most members teach
and conduct research at colleges and universities. Others conduct
research in various government laboratories, nonprofit research
institutions, and industry.
Founded in 1906, the Society is based in Bethesda, Maryland, on the
campus of the Federation of American Societies for Experimental
Biology. The Society's primary purpose is to advance the sciences of
biochemistry and molecular biology through its publications, the
Journal of Biological Chemistry, the Journal of Lipid Research,
Molecular and Cellular Proteomics, and Biochemistry and Molecular
Biology Education, and the holding of scientific meetings.
For more information about ASBMB, see the Society's website at
www.asbmb.org.
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