The effects of antiepileptic drugs on the growth of glioblastoma cell lines

Abstract

To determine the effects of antiepileptic drug compounds on glioblastoma cellular growth, we exposed glioblastoma cell lines to select antiepileptic drugs. The effects of selected antiepileptic drugs on glioblastoma cells were measured by MTT assay. For compounds showing significant inhibition, cell cycle analysis was performed. Statistical analysis was performed using SPSS. The antiepileptic compounds selected for screening included carbamazepine, ethosuximide, gabapentin, lamotrigine, levetiracetam, magnesium sulfate, oxcarbazepine, phenytoin, primidone, tiagabine, topiramate, valproic acid, and vigabatrin. Dexamethasone and temozolomide were used as a negative and positive control respectively. Our results showed temozolomide and oxcarbazepine significantly inhibited glioblastoma cell growth and reached IC50 at therapeutic concentrations. The other antiepileptic drugs screened were unable to reach IC50 at therapeutic concentrations. The metabolites of oxcarbazepine were also unable to reach IC50. Dexamethasone, ethosuximide, levetiracetam, and vigabatrin showed some growth enhancement though they did not reach statistical significance. The growth enhancement effects of ethosuximide, levetiracetam, and vigabatrin found in the study may indicate that these compounds should not be used for prophylaxis or short term treatment of epilepsy in glioblastoma. While valproic acid and oxcarbazepine were effective, the required dose of valproic acid was far above that used for the treatment of epilepsy and the metabolites of oxcarbazepine failed to reach significant growth inhibition ruling out the use of oral oxcarbazepine or valproic acid as monotherapy in glioblastoma. The possibility of using these compounds as local treatment is a future area of study.

Evaluation of the effects of antiepileptic drugs on folic acid uptake by human placental choriocarcinoma cells

“…However, 24-hour exposure to OXC and STR did not significantly alter [ 3 H]-folic acid uptake per protein, compared to the control (Table 4). OXC was shown to reduce the viability of hippocampal neurons (Morte et al, 2013), glioblastoma (Lee et al, 2016), and several cancer cell lines, such as MCF-7, HeLa, and HepG2 cells (El Sharkawi et al, 2014). The present study suggests that administration of OXC and STR during pregnancy may affect the placental development.…”

Addition of carbonic anhydrase 9 inhibitor SLC-0111 to temozolomide treatment delays glioblastoma growth in vivo

“…When we evaluated the ability of topiramate to inhibit GBM growth in the presence or absence of TMZ, we noted no additional benefit (Supplemental Figure 3), but a recent study indicated that topiramate treatment decreased intracellular pH in U87 GBM cells in vivo (47). Antiepileptic drugs including topiramate are often used for treatment of tumor-associated epilepsy, but results to determine direct efficacy against GBM cell growth in vitro have been mixed (48,49). Although several antiepileptic drugs have not demonstrated significant improvements in overall survival (50), our data suggest that further clinical evaluation of those with carbonic anhydrase inhibitor function is warranted.…”

A New Theoretical Approach for Cancer Prevention: A Novel Strategy of using Anti-Epileptic Medicines to Prevent Tumour Growth

“…These three groups includes drugs that carry out their action by blocking neuronal ion channels, the other group of drugs carry out their function by facilitating gamma-aminobutryic action [3]. The last group carries out their function in a mode that has not been resolved yet.…”

“…Phenobarbitals have also been associated with lung cancer in humans and this is in early epidemiological studies. They have also been implicated in the occurrence of brain tumours [3]. The other commonly used group of anti epileptic drugs are the phenytoin.…”

“…However it is important to note that no consistent data or results have been collected to accurately confirm that the two group of drugs are cancer causing. Phenobarbitals and phenytoins are only thought to be possible carcinogenic agents, necessitating for more medical research on the subject [3].…”