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 (2006) 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 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.
ChemLin offers different
instruments with which you can publish or refer to the appropriate web
pages, press releases, product news, appointments etc.
For your personal publication please use this form.
