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

Lee CY, Lai HY, Chiu A, Chan SH, Hsiao LP, Lee ST - J. Neurooncol. (2016)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, 5 Fu-Shing Street, 333, Kweishan, Taoyuan, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus

a The 17 compounds ordered according to maximum percent of growth inhibition after treatment using the T98 cell line with a minimum of three replicates. b The 17 compounds ordered according to maximum percent of growth inhibition after treatment using the U87 cell line with a minimum of three replicates
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Fig2: a The 17 compounds ordered according to maximum percent of growth inhibition after treatment using the T98 cell line with a minimum of three replicates. b The 17 compounds ordered according to maximum percent of growth inhibition after treatment using the U87 cell line with a minimum of three replicates

Mentions: Overall growth inhibition for all compounds and cell lines are shown in Fig. 1. Figure 2 depicts the maximum growth inhibition reached by each compound and can be separated into control compounds, non-effective compounds, and effective compounds, with effective compounds consisting of those that reached half maximal inhibitory concentration (IC50) as shown in Table 2.Fig. 1


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

Lee CY, Lai HY, Chiu A, Chan SH, Hsiao LP, Lee ST - J. Neurooncol. (2016)

a The 17 compounds ordered according to maximum percent of growth inhibition after treatment using the T98 cell line with a minimum of three replicates. b The 17 compounds ordered according to maximum percent of growth inhibition after treatment using the U87 cell line with a minimum of three replicates
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835521&req=5

Fig2: a The 17 compounds ordered according to maximum percent of growth inhibition after treatment using the T98 cell line with a minimum of three replicates. b The 17 compounds ordered according to maximum percent of growth inhibition after treatment using the U87 cell line with a minimum of three replicates
Mentions: Overall growth inhibition for all compounds and cell lines are shown in Fig. 1. Figure 2 depicts the maximum growth inhibition reached by each compound and can be separated into control compounds, non-effective compounds, and effective compounds, with effective compounds consisting of those that reached half maximal inhibitory concentration (IC50) as shown in Table 2.Fig. 1

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, 5 Fu-Shing Street, 333, Kweishan, Taoyuan, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus