gms | German Medical Science

Objective: Up to now, no effective drug or therapy regimen for the treatment of glioblastoma multiforme is available. We investigated whether the dipeptide, carnosine, might be a promising candidate.

Methods: For in vitro analyses we used the cell line T98G as well as primary cell cultures established from freshly resected glioblastomas. Cell cultures were incubated with carnosine at different concentrations. Afterwards dehydrogenase activity, cellular ATP concentration and the rate of DNA synthesis were determined. To solve the question as to whether carnosine acts at the level of glycolysis or mitochondrial oxidative phosphorylation, experiments were performed with inhibitors specific for glycolysis (oxamate) and oxidative phosphorylation (KCN).

In addition, we investigated the in vivo effects of carnosine in the HER2/NEU mouse model.

Results: The in vitro experiments demonstrated a significant dose-dependent reduction in cellular ATP and dehydrogenase activity. Carnosine reduced DNA synthesis to a rate down to 10%. The reduction of ATP production under simultaneous incubation with oxamate was not enhanced by carnosine indicating that carnosine interferes with glycolysis.

Statistical analysis of in vivo tumor growth revealed significant differences between treated and control mice.

Conclusions: Carnosine is able to inhibit proliferation of cells derived from glioblastoma multiforme. It appears to act by reducing ATP production. There is a strong indication that this effect is mediated by an interference with glycolytic ATP production. Since carnosine is able to penetrate the blood-brain-barrier and to restrict tumor growth in vivo, we consider it to be a likely candidate for the treatment of glioblastoma multiforme.