Study led by FCT researcher reveals different effects of anti-inflammatory drug on cells

The molecular effect of a large number of drugs is unknown. This is the question motivating 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 the Dr. Ricardo Jorge National Health Institute. 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 in maintaining healthy joints. Several studies have suggested that, in addition to reducing pain and thus benefiting 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 diseases has yet to be established, mainly due to the range of effects recorded, on cells and their molecules.

In the most recent edition 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 found that treatment with glucosamine leads to an increase in the transportation 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, transportation and degradation of proteins. This observation led to the interesting and surprising discovery that glucosamine, in the laboratory, protects the cancer cells used from the action of the drug Bortezomib, suggesting a more careful analysis of the relationship between drug treatment and diet.

The results now obtained contribute to unraveling the molecular mechanisms and processes that are activated in the different compartments of the cell after treatment with glucosamine, and could 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 the genes that are activated by glucosamine (using DNA chips ) - and proteomics - the study of glucosamine-induced changes in proteins (using mass spectrometry). All the raw data collected in this study is available in open access databases, freely available to researchers all over the world.

This work was fully funded by FCT, through the Investigador FCT program, various project grants and a post-doctoral Studentship , in addition to IPATIMUP being an Associate Laboratory funded by 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 flow cytometry experiments.