Tetramethylpyrazine inhibits activities of glioma cells and glutamate neuro-excitotoxicity: potential therapeutic application for treatment of gliomas.
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 muM 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 microM). Gliomaneuronal co-culturing resulted in significant neuronal damage and higher proliferation of the glioma cells (140%) compared with single cultures. Low concentrations of TMP (< or =200 microM) 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.
Fu
Yu-Show
YS
Department of Anatomy, School of Medicine, National Yang-Ming University, 155 Sec. 2 Li-Nung Street, Taipei, Taiwan. ysfu@ym.edu.tw
Lin
Yen-Yang
YY
Chou
Shih-Chich
SC
Tsai
Tung-Hu
TH
Kao
Lung-Sen
LS
Hsu
Shao-Yun
SY
Cheng
Fu-Chou
FC
Shih
Yang-Hsin
YH
Cheng
Henrich
H
Fu
Yu-Yi
YY
Wang
Jia-Yi
JY
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D005910:Glioma / Q000188:drug therapy*; D018698:Glutamic Acid / Q000633:toxicity; D017551:Microdialysis; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D011719:Pyrazines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D011719:Pyrazines; D018698:Glutamic Acid; C017953:tetramethylpyrazine