Efficiency of Anti-Epileptic Drug Topiramate in Treatment of Glioblastoma: An InVitro Perception
Journal Title: Scholars Bulletin - Year 2018, Vol 4, Issue 5
Abstract
Abstract:Brain tumors account for 85% to 90% of CNS tumors. In 20-40% of the patients suffering from brain tumor (BT), seizures are common during the commencement of the disease. The relationship between the onset of seizures and brain tumor is poorly understood. These patients show a complex therapeutic profile making selection of the drugs very tough. The quality of life of the patient is highly compromised due to brain tumor-related epilepsy (BTRE) as it is drug-resistant and poses the challenging risk factor for everlasting disability. Hence, there arise the need of unique and multidisciplinary approach of proper selection of medications with minimum side effects. GlioblastomaMultiforme is a grade IV highly malignant tumor attacking the glia, which provides nourishment and assist in signal transmission. Glioma cells secrete glutamate and choose neurotransmitter receptors for their invasive growth. Glutamate binds to ionotropic receptors, activate calcium release mediating excitatory neurotransmission. The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are the major mediators of glutamate-mediated excitatory neurotransmission and are critical for spread of epileptic activity. Glutamate is the main culprit for both the occurrence of seizures and glioma metastases. Hence there lies an opportunity to use the anti-epileptic drugs which targets calcium permeable AMPA receptors for the treatment of glioblastoma as well as BTRE. Topiramate (TPM), a derivative of D-fructose is a novel broad spectrum anti-epileptic drug which shows antagonistic effect on AMPA receptor. When treated with TPM a dose-dependent decrease in live cell number, increase in the number of apoptotic cells, decrease in the calcium influx, reduction in phosphorylation of Akt, Erk1/2 expression were observed. Also phosphorylation of AMPA receptor in presence of EGF was observed. The data suggests that topiramate lead to decrease in proliferation and survival by decreasing calcium influx and inhibiting mitogenic and survival signalling in U87MG cells. Keywords:Brain tumors, AMPA receptors, neurotransmission.
Authors and Affiliations
Sharma Arpana, Kartha Anitha, Rana Pratap Singh, Mishra J. P. N
Keywords
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