Article
L-Carnosine - a naturally occurring dipeptide with potential antitumor activity in primary cultures of glioblastoma multiforme
L-Carnosin, ein natürlich vorkommendes Dipeptid mit beträchtlicher wachstumshemmender Wirkung in Primärkulturen von Glioblastomen
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Authors
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C. Renner
- Department of Neurosurgery, University of Leipzig
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S. Garcia de Arriba
- Department of Pharmacology and Toxicology, University of Leipzig
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F. Gaunitz
- Department of Biochemistry, University of Leipzig
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J. Meixensberger
- Department of Neurosurgery, University of Leipzig
| Published: | May 4, 2005 |
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Outline
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Objective
Carnosine (β-alanyl-L-histidine) is a naturally occurring dipeptide with antioxidant activity and chelating capacity of toxic metals. Carnosine influences the lifespan of cultured cells and thus it seems to play a key role in cell maintenance. However, in 1996 Holliday and McFarland reported a selective toxicity of carnosine on human neoplastic cell lines at physiological concentrations (20mM) in dependence of glucose and / or pyruvate. The aim of this work was to investigate a possible selective toxicity on glioblastoma cells.
Methods
Primary cell cultures of 8 patients with glioblastoma multiforme were investigated. Human astroglia (LS-107) and human glia stem cell lines were used as controls. Cells were incubated with carnosine in concentrations of 20, 40 and 50mM for 5 days in the presence of different concentrations of glucose and/or pyruvate. Cell viability was assessed by MTT - and ATP – assays as well as by measuring the dehydrogenase activity. Furthermore, the mitochondrial function (Rhodamine-123 flourescence) and formation of reactive oxygen species (ROS) were measured.
Results
Carnosine significantly inhibits cell viability of glioblastoma cells in a dose-dependent manner. This toxic effect was not seen in the human astroglia cell line LS-107 nor in glia stem cells. Carnosine induced formation of ROS and it modified the mitochondrial depolarization.
Conclusions
Carnosine has a potential activity against malignant transformed brain tumor cells. The mechanism of anti tumor activity could be related to the formation of ROS and mitochondrial dysfunction. The selective effect on tumor cells suggests a possible use as a therapeutic anticancer drug, at least in the case of glioblastoma multiforme.
