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

The molecular effect 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 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 for reducing pain and inflammation and maintaining healthy joints. Several studies have suggested that, in addition to pain relief and the resulting benefits for osteoarthritis patients, glucosamine may also protect against cardiac ischemia (reduced blood flow to the heart muscle) and help destroy cancer cells. However, despite 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 latest issue of Molecular and Cellular Proteomics, Rune and his colleagues used new technologies to analyze advanced data on the proteins found in different compartments of certain cancer cells. The team discovered that treatment with glucosamine 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 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 different cell compartments 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 comprehensive approach, using transcriptomics—the analysis of all genes activated by glucosamine (using DNA chips )—and proteomics—the study of changes in proteins induced by glucosamine (using mass spectrometry). All raw data collected in this study are available in open-access databases, freely available to researchers worldwide.

This work was fully funded by FCT, through the FCT Investigator program, various project grants, and a Studentship , in addition to IPATIMUP being an Associate Laboratory by FCT. Several research centers contributed to the study: the Gulbenkian Institute of Science (IGC) provided DNA chip services, and the Institute of Molecular and Cellular Biology (IBMC) supported the experiments carried out with flow cytometry.