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Lidocaine suppresses glioma cell proliferation by inhibiting TRPM7 channels
Tiandong Leng1, Suizhen Lin2, Zhigang Xiong1
1Neurobiology, Neuroscience Institute, Morehouse School of MedicineAtlanta GA 30329, USA.
Background:
Malignant glioma is the most common brain cancer with devastating prognosis. Recurrence of malignant glioma following surgery is very common with few preventive and therapeutic options. Novel targets and therapeutic agents are constantly sought for better outcome. Our previous study established that inhibition of transient receptor potential melastatin 7 (TRPM7) channels resulted in significant decrease of human glioma cell growth and proliferation. As local anesthetic lidocaine has been shown to inhibit TRPM7 currents, we hypothesize that lidocaine may suppress glioma cell proliferation through TRPM7 channel inhibition.
Methods:
TRPM7 currents were recorded in rat C6 glioma cells using the whole cell patch clamp technique. Cell growth and proliferation were assessed under microscopic examination and biochemical assays.
Results:
Lidocaine inhibits TRPM7-like currents in a dose-dependent and reversible manner. At 1 and 3 mM, it inhibits ~30% and ~50% of TRPM7 currents. At these concentrations, it is effective in inhibiting the proliferation of C6 cells. As expected, the TRPM7 inhibitors gadolinium and 2-Aminoethoxydiphenyl borate have similar effects on TRPM7 currents and proliferation of C6 cells. Similar to its effect on C6 cells, lidocaine inhibits the proliferation of A172 cells, a human glioblastoma cell line.
Conclusions:
Lidocaine significantly inhibits the proliferation of glioma cells. The effect of lidocaine is mediated, at least in part, by inhibiting TRPM7 channels.
Insights
Local anesthetic lidocaine suppresses glioma cell growth by inhibiting TRPM7 channels. This finding offers a potential new therapeutic strategy for malignant glioma, a common and aggressive brain cancer.
Area of Science:
- Neuroscience
- Oncology
- Pharmacology
Background:
- Malignant glioma is a prevalent brain cancer with a poor prognosis and high recurrence rates.
- Current therapeutic options for glioma are limited, necessitating the search for novel targets and treatments.
- Previous research indicated that inhibiting transient receptor potential melastatin 7 (TRPM7) channels reduces glioma cell growth.
Purpose of the Study:
- To investigate the potential of lidocaine, a local anesthetic known to inhibit TRPM7 currents, as a suppressor of glioma cell proliferation.
- To determine if lidocaine exerts its anti-glioma effects through the inhibition of TRPM7 channels.
Main Methods:
- Whole-cell patch clamp electrophysiology was used to record TRPM7 currents in rat C6 glioma cells.
- Cell proliferation was assessed using microscopic examination and biochemical assays.
- The effects of lidocaine, gadolinium, and 2-Aminoethoxydiphenyl borate on TRPM7 currents and cell proliferation were evaluated.
Main Results:
- Lidocaine demonstrated dose-dependent and reversible inhibition of TRPM7-like currents in glioma cells.
- Lidocaine (1-3 mM) significantly inhibited the proliferation of both C6 glioma and A172 human glioblastoma cells.
- TRPM7 inhibitors gadolinium and 2-Aminoethoxydiphenyl borate produced similar effects on TRPM7 currents and cell proliferation.
Conclusions:
- Lidocaine effectively inhibits the proliferation of glioma cells.
- The anti-proliferative effect of lidocaine on glioma cells is, at least partly, mediated by the inhibition of TRPM7 channels.
- Lidocaine represents a potential therapeutic agent for malignant glioma targeting TRPM7.
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