In vitro antineoplastic effects of brivaracetam and lacosamide on human glioma cells

Abstract

BackgroundEpilepsy is a frequent symptom in patients with glioma. Although treatment with antiepileptic drugs is generally effective in controlling seizures, drug-resistant patients are not uncommon. Multidrug resistance proteins (MRPs) and P-gp are over-represented in brain tissue of patients with drug-resistant epilepsy, suggesting their involvement in the clearance of antiepileptic medications. In addition to their anticonvulsant action, some drugs have been documented for cytotoxic effects. Aim of this study was to evaluate possible in vitro cytotoxic effects of two new-generation antiepileptic drugs on a human glioma cell line U87MG.MethodsCytotoxicity of brivaracetam and lacosamide was tested on U87MG, SW1783 and T98G by MTS assay. Expression of chemoresistance molecules was evaluated using flow cytometry in U87MG and human umbilical vein endothelial cells (HUVECs). To investigate the putative anti-proliferative effect, apoptosis assay, microRNA expression profile and study of cell cycle were performed.ResultsBrivaracetam and lacosamide showed a dose-dependent cytotoxic and anti-migratory effects. Cytotoxicity was not related to apoptosis. The exposure of glioma cells to brivaracetam and lacosamide resulted in the modulation of several microRNAs; particularly, the effect of miR-195-5p modulation seemed to affect cell cycle, while miR-107 seemed to be implicated in the inhibition of cells migration. Moreover, brivaracetam and lacosamide treatment did not modulate the expression of chemoresistance-related molecules MRPs1-3-5, GSTπ, P-gp on U87MG and HUVECs.ConclusionBased on antineoplastic effect of brivaracetam and lacosamide on glioma cells, we assume that patients with glioma could benefit by the treatment with these two molecules, in addition to standard therapeutic options.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0546-9) contains supplementary material, which is available to authorized users.

Lacosamide at therapeutic concentrations induces histone hyperacetylation in vitro

“…), although mild, is in line with recent data from glioma cell lines, although it has been attributed to CRMP2 inhibition . Others have demonstrated lacosamide‐induced interference of cell cycle and inhibition of cell migration . These findings suggest that lacosamide should be further evaluated as an antineoplastic agent.…”

Epilepsy biomarkers – Toward etiology and pathology specificity

“…In addition to identifying pharmacodynamic/response plasma and brain biomarkers that would indicate the target engagement, blood biomarker analyses can be compromised by AEDs. For example, valproic acid (Wang et al, 2017), brivaracetam, lacosamide (Rizzo et al, 2017), and phenobarbital (Koufaris et al, 2013) regulate miRNA expression. On the other hand, non-AED treatments, such as aspirin, can also affect the analyses (de Boer et al, 2013).…”

A brain glioma gene delivery strategy by angiopep-2 and TAT-modified magnetic lipid-polymer hybrid nanoparticles

“…The cytotoxicity was evaluated by MTS assay. 37 Briey, hCMEC/D3 and C6 cells were separately seeded in two 96-well plates at a density of 5 Â 10 3 cells per well, and incubated at 37 C for 24 h. Then, Ang-TAT-Fe 3 O 4 -pDNA-(ss)373 LPNPs were diluted with PBS (pH 7.4) to 50 mg mL À1 , 100 mg mL À1 , 150 mg mL À1 , 200 mg mL À1 , 300 mg mL À1 , and 400 mg mL À1 . Each concentration of the Ang-TAT-Fe 3 O 4 -pDNA-(ss)373 LPNPs was added to six wells of each 96-well plate.…”