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

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.

Tetramethylpyrazine-mediated suppression of C6 gliomas involves inhibition of chemokine receptor CXCR4 expression

“…Our data show that tumour growth is significantly inhibited in rats treated with TMPH compared with the control, which is in agreement with previous reports (10,18). Consistent with our in vitro results with C6 glioma cells, the expression of CXCR4 is abolished in C6 glioma cell implantation after TMPH treatment.…”

“…4B). These data are consistent with a previous report on the effects of TMP treatment in a rat model of C6 glioma (10). Consistent with our results from C6 glioma cells in vitro, TMPH downregulates CXCR4 in glioma implantation compared with the control (Fig.…”

“…Clinical evidence has confirmed that combining TMPH or Chuanxiong with other treatments can significantly attenuate multidrug resistance (MDR) of chemotherapy and increase the sensitivity of cancer cells to radiation in such cancers as nasopharyngeal, lung, breast, renal and ovarian cancer (7)(8)(9). Wang et al also confirmed by glioma-neuronal co-culturing that TMP could inhibit the viability of glioma cells while protecting hippocampal neurons and TMP could promote the regression of malignant gliomas in vivo (10). Therefore, TMP may be a potential therapeutic agent for the treatment of gliomas.…”

Tetramethylpyrazine Attenuates Transdifferentiation of TGF-β2–Treated Human Tenon's Fibroblasts

“…[14][15][16][17][18]29 Clinical studies also suggest that TMP shows promise as complementary therapy for various Images were captured by a confocal laser scanning microscope (Zeiss LSM 510). F-actin content was quantified using Zeiss LSM 510 Examiner software and normalized by cell number to evaluate stress fiber formation.…”

“…Several studies demonstrated that TMP has multiple pharmacologic activities, including suppressing tumor growth, inhibiting neovascularization, and attenuating pathologic fibrosis. [14][15][16][17] In vivo and in vitro studies indicate that TMP protects the liver from CCl4-induced fibrogenesis by modulating the NLRP3 inflammasome pathway 18 ; and our previous studies in rats demonstrated that TMP protects against pulmonary bleomycininduced fibrosis by modulating the SDF-1/CXCR4 axis. 16 Studies in the liver suggest that TMP likely exerts antifibrotic effects by inhibiting Smad2/3 expression; and in hypoxic myocardial cells, protective doses of TMP downregulated the p38 MAPK pathway.…”