Study led by FCT researcher reveals differentiated effects of anti-inflammatory drug in the cell

The effect, at the molecular level, of a large number of drugs is unknown. This is the question that motivates the research of Rune Matthiesen, a Danish FCT researcher, working at the Institute of Molecular Pathology and Immunology (IPATIMUP) at the University of Porto and at the National Institute of Health Dr. Ricardo Jorge. Glucosamine supplements are an example of such drugs. They are a popular and safe alternative to non-steroidal drugs in reducing pain and inflammation, and maintaining healthy joints. Several studies have suggested that in addition to pain mitigation and consequent benefit for osteoarthritis patients, glucosamine may also protect against cardiac ischemia (reduced blood flow to the heart muscle) and help destroy cancer cells. However, despite the promising results, a clear molecular effect for glucosamine in the treatment of disease has yet to be established, mainly due to the range of effects recorded, on cells and their molecules.

In the latest issue of the journal Molecular and Cellular Proteomics, Rune and his colleagues used new technologies to analyze advanced data on the proteins in the different compartments of certain cancer cells. The team discovered that glucosamine treatment leads to an increase in the transport of proteins to their destinations. By comparing protein production and gene expression, they concluded that glucosamine acts on the process that controls the birth, assembly, transport and degradation of proteins. This observation led to the interesting and surprising finding that glucosamine, in the laboratory, protects used cancer cells from the action of the drug Bortezomib, suggesting a closer look at the relationship between pharmacological treatment and diet.

The results now obtained contribute to unraveling the molecular mechanisms and processes that are activated in different compartments of the cell after treatment with glucosamine, and may lead to the discovery of new targets for the treatment of cardiovascular diseases, diabetes, and cancer.

The team adopted a global approach, using transcriptomics - the analysis of all genes that are activated by glucosamine (using DNA chips ) - and proteomics - study of the modifications in proteins, induced by glucosamine (through mass spectrometry technique). All the raw data collected in this study are available in open access databases, freely available to researchers around the world.

This work was fully funded by the FCT, through the FCT Investigator program, several project funding and a Studentship post-doctoral fellowship, in addition to IPATIMUP being a Associate Laboratory funded by the FCT. Several research centers contributed to the study: the Instituto Gulbenkian de Ciência (IGC) provided the DNA chip service, and the Instituto de Biologia Molecular e Celular (IBMC) supported the experiments performed with flow cytometry.