Anti-tumor effects of perampanel in malignant glioma cells

by Selleckchem | Jul 05 2023

Glioblastoma has a poor prognosis even after multimodal treatment, such as surgery, chemotherapy and radiation therapy. Patients with glioblastoma frequently develop epileptic seizures during the clinical course of the disease and often require antiepileptic drugs. Therefore, agents with both antiepileptic and antitumoral effects may be very useful for glioblastoma treatment. Perampanel, an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist, is an antiepileptic drug that is widely used for intractable epilepsy. The present study aimed to assess the potential antitumoral effects of perampanel using malignant glioma cell lines. The cell proliferation inhibitory effect was evaluated using six malignant glioma cell lines (A-172, AM-38, T98G, U-138MG, U-251MG and YH-13). A dose-dependent inhibitory effect of perampanel on cell viability was demonstrated; however, the sensitivity of cells to perampanel varied and further antitumoral effects were demonstrated in combination with temozolomide (TMZ) in certain malignant glioma cells. Furthermore, cell cycle distribution and apoptosis induction analyses were performed in T98G and U-251MG cells using a fluorescence activated cell sorter (FACS) and the expression levels of apoptosis-related proteins were evaluated using western blotting. No significant change was demonstrated in the proportions of cells in the G0/G1, S and G2/M phases under 1.0 µM perampanel treatment, whereas induction of apoptosis was demonstrated using FACS at 10 µM perampanel and western blotting at 1.0 µM perampanel in both glioma cell lines. Overexpression of SERPINE1 may be related to poor prognosis in patients with gliomas. The combination of 1.0 µM perampanel and 5.0 µM tiplaxtinin, a SERPINE1 inhibitor, demonstrated further reduced cell viability in perampanel-resistant U-138MG cells, which have high expression levels of SERPINE1. These results indicated that the antitumor effect of perampanel may not be expected for malignant gliomas with higher expression levels of SERPINE1. The findings of the present study suggested that the antiepileptic drug perampanel may also have an antitumor effect through the induction of apoptosis, which is increased when combined with TMZ in certain malignant glioma cells. These findings also suggested that SERPINE1 expression may be involved in perampanel susceptibility. These results may lead to new therapeutic strategies for malignant glioma.

Comments:

The present study investigated the potential antitumoral effects of perampanel, an antiepileptic drug, on malignant glioma cell lines. The researchers evaluated the inhibitory effect of perampanel on cell viability using six different glioma cell lines. They found that perampanel had a dose-dependent inhibitory effect on cell viability, although the sensitivity of the cells to perampanel varied among the different cell lines.

Interestingly, the study also demonstrated additional antitumoral effects when perampanel was combined with temozolomide (TMZ) in certain malignant glioma cells. This suggests that the combination of perampanel and TMZ may be more effective in treating glioblastoma compared to using either drug alone.

To further understand the mechanism of action, the researchers analyzed cell cycle distribution and apoptosis induction in two glioma cell lines, T98G and U-251MG, using a fluorescence activated cell sorter (FACS). They observed that perampanel treatment did not significantly alter the proportions of cells in different cell cycle phases at a concentration of 1.0 µM. However, apoptosis induction was observed at a concentration of 10 µM using FACS and at 1.0 µM using western blotting in both cell lines. This suggests that perampanel may induce apoptosis in glioma cells, which can contribute to its antitumoral effects.

The study also investigated the expression levels of apoptosis-related proteins and the role of SERPINE1 (also known as PAI-1), a protein associated with poor prognosis in gliomas. The results indicated that the combination of perampanel and tiplaxtinin, a SERPINE1 inhibitor, further reduced cell viability in perampanel-resistant U-138MG cells with high expression levels of SERPINE1. This suggests that perampanel may not be effective in gliomas with higher expression levels of SERPINE1.

Overall, the findings of this study suggest that perampanel, an antiepileptic drug, may also have antitumoral effects in malignant gliomas. It can induce apoptosis in glioma cells, especially when combined with TMZ. However, the efficacy of perampanel may be influenced by the expression levels of SERPINE1 in gliomas. These findings provide insights into potential therapeutic strategies for the treatment of malignant gliomas.