Tetramethylpyrazine inhibits activities of glioma cells and glutamate neuro-excitotoxicity: Potential therapeutic application for treatment of gliomas

Yu Show Fu, Yen Yang Lin, Shih Chich Chou, Tung Hu Tsai, Lung Sen Kao, Shao Yun Hsu, Fu Chou Cheng, Yang Hsin Shih, Henrich Cheng, Yu Yi Fu, Jia Yi Wang

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38 Citations (Scopus)

Abstract

We tested the herbal extract 2,3,5,6-tetramethylpyra-zine (TMP) for possible therapeutic efficacy against a glioma cell line and against gliomas transplanted into rat brains. In the cultured glioma cells, 50 μM TMP significantly inhibited glutamate-induced increase in intracellular calcium. Significant cell damage (30%) and proliferation suppression (10%), however, occurred only at higher concentrations (200-400 μM). Glioma-neuronal co-culturing resulted in significant neuronal damage and higher proliferation of the glioma cells (140%) compared with single cultures. Low concentrations of TMP (≤200 μM) attenuated the neuronal damage, suppressed glioma migration, and decreased glioma proliferation in the neuronal-glioma co-culture. Gliomas transplanted into the frontal cortical area exhibited high proliferation, with untreated rats dying 10-23 days later. TMP treatment inhibited tumor growth and significantly extended survival time. The results indicate that TMP can suppress glioma activity, including growth, and protect neurons against glioma-induced excitotoxicity, suggesting that TMP may have therapeutic potential in the treatment of malignant gliomas.

Original languageEnglish
Pages (from-to)139-152
Number of pages14
JournalNeuro-Oncology
Volume10
Issue number2
DOIs
Publication statusPublished - Apr 2008
Externally publishedYes

Keywords

  • Calcium
  • Excitotoxicity
  • Glioblastoma multiforme
  • Tetramethylpyrazine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

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  • Cite this

    Fu, Y. S., Lin, Y. Y., Chou, S. C., Tsai, T. H., Kao, L. S., Hsu, S. Y., Cheng, F. C., Shih, Y. H., Cheng, H., Fu, Y. Y., & Wang, J. Y. (2008). Tetramethylpyrazine inhibits activities of glioma cells and glutamate neuro-excitotoxicity: Potential therapeutic application for treatment of gliomas. Neuro-Oncology, 10(2), 139-152. https://doi.org/10.1215/15228517-2007-051