ABSTRACT
BACKGROUND: Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor with a dismal prognosis. Despite intensive study on tumor biology, the underlying mechanisms of the unlimited proliferation and progressive local invasion are still poorly understood, and no effective treatment has been developed for GBM patients. AIMS: We determine the role of TRPM7 channels in the growth, migration, and infiltration of malignant glioma cells. METHODS: Using a combination of RT-PCR, Western blot, and patch-clamp techniques, we demonstrated the expression of functional TRPM7 channels of A172 cells, a human glioma cell line, as well as in human glioma tissues. Furthermore, we evaluated the role of TRPM7 in growth, migration, and infiltration of A172 cells with MTT and transwell migration and invasion assays. RESULTS: We showed the expression of functional TRPM7 channels in both A172 cells and human glioma tissues. Suppression of TRPM7 expression with TRPM7-siRNA dramatically reduced the proliferation, migration, and invasion of A172 cells. Pharmacological inhibition of TRPM7 channel with 2-aminoethoxydiphenyl borate (2-APB) showed a similar effect as TRPM7-siRNA. CONCLUSION: We demonstrate that human glioma cells express functional TRPM7 channel and that activation of this channel plays an important role in the proliferation, migration, and invasion of malignant glioma cells. TRPM7 channel may represent a novel and promising target for therapeutic intervention of malignant glioma.
Subject(s)
Brain Neoplasms/physiopathology , Cell Movement/drug effects , Cell Proliferation/drug effects , Glioblastoma/physiopathology , Neoplasm Invasiveness/physiopathology , Protein Serine-Threonine Kinases/antagonists & inhibitors , TRPM Cation Channels/antagonists & inhibitors , Blotting, Western , Boron Compounds/pharmacology , Brain Neoplasms/drug therapy , Cell Line, Tumor , Cell Movement/physiology , Cell Proliferation/physiology , Cells, Cultured , Glioblastoma/drug therapy , Humans , Patch-Clamp Techniques , Polymerase Chain Reaction , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , RNA, Messenger/metabolism , RNA, Small Interfering , TRPM Cation Channels/genetics , TRPM Cation Channels/metabolismABSTRACT
Monosodium glutamate (MSG), a common flavor enhancer in various canned food and stereotypically associated with food in Chinese restaurants, has been claimed and tested to have side effects including headache and dizziness. However, the mechanism behind MSG-induced headache was not clear. Using dissociated mouse neuronal culture and cell injury assays, we determined whether incubation of neurons with clinically relevant concentrations of MSG induces cell swelling or death, and whether any measure can be taken to prevent or reduce MSG effects. We demonstrated that (1) Treatment with MSG induces a dose-dependent swelling and death of mature neurons (12-14 days in culture) with little effect on young immature neurons (<1 week in culture). The threshold concentration of MSG for neuronal injury is 3 microM; (2) MSG only injures neurons with little effect on glial cells; (3) Boiling MSG does not affect its toxicity but the addition of Vitamin C provides significant protection against MSG toxicity; (4) Pretreatment of neurons with a low dose of MSG reduces subsequent injury by a large dose of MSG. Together, our studies suggest that the side effect of MSG may be mediated, at least in part, by its toxic effect on brain neurons. Pre-exposure to low doses of MSG or the use of Vitamin C may prevent or reduce the side effects of MSG.
