Lidocaine suppresses glioma cell proliferation by inhibiting TRPM7 channels

Int J Physiol Pathophysiol Pharmacol. 2017 Apr 15;9(2):8-15. eCollection 2017.


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.

Keywords: Lidocaine; TRPM7; glioma; local anesthetic; proliferation.