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

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.

	Abstract

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

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. A. Grossman, X. Ye, M. Chamberlain, T. Mikkelsen, T. Batchelor, S. Desideri, S. Piantadosi, J. Fisher, and H. A. Fine Talampanel With Standard Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma: A Multicenter Phase II Trial J. Clin. Oncol., September 1, 2009; 27(25): 4155 - 4161. [Abstract] [Full Text] [PDF]

				R. Roesler, N. Schroder, and G. Schwartsmann LETTER TO THE EDITOR Neuro-oncol, January 1, 2009; 11(2): 236 - 237. [Full Text] [PDF]