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Carnosine Inhibits Growth of Cells Isolated from Human Glioblastoma Multiforme

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Abstract

The present study evaluates the effect of the naturally occurring dipeptide carnosine on primary cell cultures established from patients with glioblastoma multiforme. Surgically removed tumors were used to establish primary cell cultures that were incubated for 96 h with medium supplemented with carnosine at concentrations of 20, 40 and 50 mM. Following incubation, dehydrogenase activity, cellular adenosine triphosphate concentration (ATP), caspase activity, lactate dehydrogenase (LDH) release and the rate of DNA synthesis were determined. After 96 h of carnosine treatment a significant reduction in cellular ATP and dehydrogenase activity was detected already at a concentration of 20 mM carnosine. Carnosine (50 mM) reduced ATP concentration to 42.7 ± 13.5% (n = 6) and dehydrogenase activity to 41.0 ± 19.3% (n = 6) compared to untreated cells. Additional experiments revealed no sign of enhanced apoptosis or necrosis in the presence of carnosine. However, a quantitative bromo-desoxy-uridine-based proliferation assay demonstrated a clear effect of carnosine on DNA synthesis reducing its rate down to 50% (2 cultures) and 10% (4 cultures). Therefore, it can be concluded that carnosine is obviously able to inhibit proliferation of cells derived from glioblastoma. Since it is a naturally occurring substance that appears to be non-toxic to normal tissue and is able to penetrate the blood–brain barrier it may be a candidate for a therapeutic agent that may reduce proliferation of neoplastic cells even in vivo and especially in cases of glioblastoma multiforme.

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Acknowledgement

We would like to thank Mr. Baran-Schmidt for technical assistance in preparing the primary cultures of glioblastomas.

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Authors and Affiliations

  1. Klinik und Poliklinik für Neurochirurgie, Medizinische Fakultät der Universität Leipzig, 04103, Leipzig, Germany

    Christof Renner & Jürgen Meixensberger

  2. Institut für Biochemie, Medizinische Fakultät der Universität Leipzig, Johannisallee 30, 04103, Leipzig, Germany

    Anne Seyffarth, Rolf Gebhardt & Frank Gaunitz

  3. Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Medizinische Fakultät der Universität Leipzig, 04103, Leipzig, Germany

    Susana Garcia de Arriba

Authors
  1. Christof Renner
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  2. Anne Seyffarth
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  3. Susana Garcia de Arriba
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  4. Jürgen Meixensberger
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  5. Rolf Gebhardt
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  6. Frank Gaunitz
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Correspondence to Frank Gaunitz.

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Renner, C., Seyffarth, A., de Arriba, S.G. et al. Carnosine Inhibits Growth of Cells Isolated from Human Glioblastoma Multiforme. Int J Pept Res Ther 14, 127–135 (2008). https://doi.org/10.1007/s10989-007-9121-0

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  • DOI: https://doi.org/10.1007/s10989-007-9121-0

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