© Copyright 2008 by the Society for Neuro-Oncology
Received August 21, 2006
Accepted April 5, 2007
Basic and Translational Investigations
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Tetramethylpyrazine inhibits activities of glioma cells and glutamate neuro-excitotoxicity: Potential therapeutic application for treatment of gliomas
Yu-Show Fu 1*,
Yen-Yang Lin 2,
Shih-Chich Chou 2,
Tung-Hu Tsai 3,
Lung-Sen Kao 4,
Shao-Yun Hsu 2,
Fu-Chou Cheng 5,
Yang-Hsin Shih 6,
Henrich Cheng 7,
Yu-Yi Fu 8,
Jia-Yi Wang 9
1 Department of Anatomy, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Education and Research, Taipei City Hospital, Taipei, Taiwan
2 Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
3 Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Education and Research, Taipei City Hospital, Taipei, Taiwan
4 Faculty of Life Sciences, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan
5 Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
6 Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, Taipei Medical University, Taipei, Taiwan
7 Department of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Neural Regeneration Laboratory and Center for Neural Regeneration, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan
8 Department of Automation Engineering, Nan Kai Institute of Technology, Nantou, Taiwan
9 Department of Physiology, National Defense University, Taipei, Taiwan
* To whom correspondence should be addressed. E-mail: ysfu{at}ym.edu.tw.
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Abstract |
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We tested the herbal extract 2,3,5,6-tetramethylpyrazine (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 %M) 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.
Key Words:
calcium, excitotoxicity, glioblastoma multiforme, tetramethylpyrazine
