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Iron-metabolising enzyme key to Kaposi therapy

By Wai Lang Chu , 24-Apr-2006

Scientists think that their latest discovery could result in the production of new drugs to treat Kaposi sarcoma tumour growth, which is the most frequent tumour in AIDS patients and is caused by infection of the patients with the Kaposi sarcoma-associated herpes virus.

The scientists found that inhibition of heme oxygenase-1, an enzyme involved in iron metabolism, reduces Kaposi sarcoma tumour growth and represents a new anticancer tactic in the tumour's treatment as well as generate potential clinical interest.

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.

Study author Maria Julia Marinissen of the Universidad Autonoma de Madrid. and her colleagues found that vGPCR increases production of the heme oxygenase-1 protein and the RNA that codes for it.

They also discovered that mice with tumours that were given specific pharmacological inhibitors that blocked heme oxygenase-1 activity showed a significant reduction in tumor growth without apparent side effects.

"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," said Marinissen.

"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."

A previous 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,"

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.

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