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PMID: 18314418 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Neuro-oncology ·Vol. 10 ·No. 2 ·2008-04-00 ·Pages 139-52

Fu YS, Lin YY, Chou SC, Tsai TH, Kao LS, Hsu SY, Cheng FC, Shih YH, Cheng H, Fu YY, Wang JY

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 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.

MeSH Terms
Animals Antineoplastic Agents/therapeutic use Brain Neoplasms/drug therapy Cell Line, Tumor Cell Movement/drug effects Cell Proliferation/drug effects Coculture Techniques Glioma/drug therapy Glutamic Acid/toxicity Microdialysis Nerve Degeneration/chemically induced,prevention & control Neurons/drug effects,pathology Pyrazines/therapeutic use Rats Rats, Sprague-Dawley Xenograft Model Antitumor Assays
Chemicals
Antineoplastic Agents Pyrazines Glutamic Acid tetramethylpyrazine
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Fu Yu-Show
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
Chou Shih-Chich
Tsai Tung-Hu
Kao Lung-Sen
Hsu Shao-Yun
Cheng Fu-Chou
Shih Yang-Hsin
Cheng Henrich
Fu Yu-Yi
Wang Jia-Yi
References (42)
42 references, click to expand
  1. Growth stimulation of human keratinocytes by tissue inhibitor of metalloproteinases.
    J Invest Dermatol. 1991 Oct;97(4):679-85 PMID: 1940438
  2. Molecular characterization and expression of the gene encoding human erythroid-potentiating activity.
    Nature. 1985 Jun 27-Jul 3;315(6022):768-71 PMID: 3839290
  3. Kainic acid-induced lipid peroxidation: protection with butylated hydroxytoluene and U78517F in primary cultures of cerebellar granule cells.
    Brain Res. 1993 Oct 8;624(1-2):223-32 PMID: 8252395
  4. Effect of tetramethylpyrazine on potassium channels to lower calcium concentration in cultured aortic smooth muscle cells.
    Clin Exp Pharmacol Physiol. 2003 Oct;30(10):793-8 PMID: 14516420
  5. Control of rat C6 glioma cell proliferation: uncoupling of the inhibitory effects of hydrocortisone hormone in suspension and monolayer cultures.
    J Cell Biol. 1983 Aug;97(2):455-8 PMID: 6350318
  6. Generation of lipid radicals in the hippocampal extracellular space during kainic acid-induced seizures in rats.
    Epilepsy Res. 1997 Jan;26(2):329-33 PMID: 9095394
  7. Pharmacokinetics of tetramethylpyrazine in rat blood and brain using microdialysis.
    Int J Pharm. 2001 Mar 23;216(1-2):61-6 PMID: 11274807
  8. [Effect of tetramethyl pyrazine on coronary vasoconstriction induced by endothelin-1 in dogs].
    Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1996 Apr;18(2):133-7 PMID: 9208604
  9. Glutamate receptor activation can trigger electrical activity in human glioma cells.
    Eur J Neurosci. 1998 Jun;10(6):2153-62 PMID: 9753101
  10. Blockage of Ca(2+)-permeable AMPA receptors suppresses migration and induces apoptosis in human glioblastoma cells.
    Nat Med. 2002 Sep;8(9):971-8 PMID: 12172541
  11. Protective effects of tetramethylpyrazine on kainate-induced excitotoxicity in hippocampal culture.
    Neuroreport. 2002 Mar 25;13(4):515-9 PMID: 11930173
  12. Tetramethylpyrazine for treatment of experimentally induced stroke in Mongolian gerbils.
    Stroke. 1989 Jan;20(1):96-9 PMID: 2911841
  13. Oxidative stress induced by glutamate receptor agonists.
    Brain Res. 1993 May 7;610(2):229-33 PMID: 8319085
  14. GFA expression in aggregation cultures of rat C6 glioma.
    Experientia. 1979 Sep 15;35(9):1170-1 PMID: 488267
  15. Inhibition of vasoconstriction by tetramethylpyrazine: does it act by blocking the voltage-dependent Ca channel?
    J Cardiovasc Pharmacol. 1990 Jan;15(1):157-62 PMID: 1688974
  16. Mammary carcinoma cells over-expressing tissue inhibitor of metalloproteinases-1 show enhanced vascular endothelial growth factor expression.
    Int J Cancer. 1998 Jan 5;75(1):81-7 PMID: 9426694
  17. Formation of free hydroxyl radicals after pentylenetetrazol-induced seizure and kindling.
    Brain Res. 1999 Nov 20;847(2):347-51 PMID: 10575107
  18. [Protective effect of tetramethylpyrazine on ischemic neuronal damage in the gerbil hippocampus].
    No To Shinkei. 1994 Sep;46(9):841-6 PMID: 7999441
  19. Inhibitory mechanisms of tetramethylpyrazine in middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in rats.
    Planta Med. 2006 Apr;72(5):411-7 PMID: 16557454
  20. Plant-derived drugs acting on cellular Ca2+ mobilization in vascular smooth muscle: tetramethylpyrazine and tetrandrine.
    Stem Cells. 1994 Jan;12(1):64-7 PMID: 8142921
  21. Oxidative mechanisms involved in kainate-induced cytotoxicity in cortical neurons.
    Neurochem Res. 1994 Dec;19(12):1557-64 PMID: 7877729
  22. Sources of reactive oxygen species production in excitotoxin- stimulated cerebellar granule cells.
    Biochem Biophys Res Commun. 1999 Mar 16;256(2):320-4 PMID: 10079182
  23. Iron-induced oxidative damage and apoptosis in cerebellar granule cells: attenuation by tetramethylpyrazine and ferulic acid.
    Eur J Pharmacol. 2003 Apr 25;467(1-3):41-7 PMID: 12706453
  24. Differential expression and localization of TIMP-1 and TIMP-4 in human gliomas.
    Br J Cancer. 2001 Jul 6;85(1):55-63 PMID: 11437402
  25. Glutamate receptors and the induction of excitotoxic neuronal death.
    Prog Brain Res. 1994;100:47-51 PMID: 7938533
  26. Glioma cells release excitotoxic concentrations of glutamate.
    Cancer Res. 1999 Sep 1;59(17):4383-91 PMID: 10485487
  27. Effects of tetramethylpyrazine on the release of PGI2 and TXA2 in the hypoxic isolated rat heart.
    Mol Cell Biochem. 1997 Feb;167(1-2):153-8 PMID: 9059992
  28. Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats.
    Neurochem Int. 2006 Feb;48(3):166-76 PMID: 16316708
  29. Mechanisms responsible for the in vitro relaxation of ligustrazine on porcine left anterior descending coronary artery.
    Eur J Pharmacol. 2003 May 16;468(3):199-207 PMID: 12754058
  30. Gene therapy of experimental brain tumors using neural progenitor cells.
    Nat Med. 2000 Apr;6(4):447-50 PMID: 10742153
  31. Ultrastructural localization and fluctuation in the level of the proliferating cell nuclear antigen and myc oncoproteins in synchronized neuroblastoma cells.
    Cancer Res. 1993 Apr 15;53(8):1899-905 PMID: 8096797
  32. Tetramethylpyrazine, a calcium antagonist.
    Planta Med. 1996 Oct;62(5):431-5 PMID: 8923809
  33. [Effects of tetramethylpyrazine on the cardiovascular system].
    Sheng Li Ke Xue Jin Zhan. 1992 Oct;23(4):313-7 PMID: 1338806
  34. Studies on single-cell adhesion probability between lymphocytes and endothelial cells with micropipette technique.
    Microvasc Res. 2002 Mar;63(2):218-26 PMID: 11866545
  35. [Effect of tetramethylpyrazine in inhibiting respiratory burst of polymorphonuclears and scavenging oxygen free radicals].
    Zhongguo Zhong Xi Yi Jie He Za Zhi. 1994 Oct;14(10):607-9 PMID: 7719095
  36. Pharmacological blockade of group II metabotropic glutamate receptors reduces the growth of glioma cells in vivo.
    Neuro Oncol. 2005 Jul;7(3):236-45 PMID: 16053698
  37. Tetramethylpyrazine scavenges superoxide anion and decreases nitric oxide production in human polymorphonuclear leukocytes.
    Life Sci. 2003 Apr 18;72(22):2465-72 PMID: 12650854
  38. Time course of transient expression of GDNF protein in rat granule cells of the bilateral dentate gyri after unilateral intrahippocampal kainic acid injection.
    Neurosci Lett. 1999 Mar 12;262(3):215-8 PMID: 10218894
  39. Ligustrazine is a vasodilator of human pulmonary and bronchial arteries.
    Eur J Pharmacol. 1990 Dec 4;191(3):345-50 PMID: 2086247
  40. The antiplatelet activity of tetramethylpyrazine is mediated through activation of NO synthase.
    Life Sci. 2000 Jul 14;67(8):937-47 PMID: 10946853
  41. Calcium-dependent free radical generation in cultured retinal neurons injured by kainate.
    Neurosci Lett. 1995 Sep 22;198(1):13-6 PMID: 8570085
  42. Glutamate release promotes growth of malignant gliomas.
    Nat Med. 2001 Sep;7(9):1010-5 PMID: 11533703
Article Info
Journal
Neuro-oncology
Abbr.
Neuro Oncol
ISSN
1522-8517
DOI
10.1215/15228517-2007-051
Email
ysfu@ym.edu.tw
Published
2008-04-00
Epub
2008-00-26
Pages
139-52
Language
English
Region
England
NLM ID
100887420
PMCID
PMC2613816
Subset
IM
Corrections
CommentIn
PMID: 19033424
External Links
PubMed source DOI: 10.1215/15228517-2007-051 PMC Full Text View journal details
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