Anti‑tumor effects of perampanel in malignant glioma cells

Tatsuoka,Juri; Sano,Emiko; Hanashima,Yuya; Yagi,Chihiro; Yamamuro,Shun; Sumi,Koichiro; Hara,Hiroyuki; Takada,Kazuhide; Kanemaru,Kazunori; Komine‑Aizawa,Shihoko; Katayama,Yoichi; Yoshino,Atsuo

doi:10.3892/ol.2022.13541

Anti‑tumor effects of perampanel in malignant glioma cells

Authors:
- Juri Tatsuoka
- Emiko Sano
- Yuya Hanashima
- Chihiro Yagi
- Shun Yamamuro
- Koichiro Sumi
- Hiroyuki Hara
- Kazuhide Takada
- Kazunori Kanemaru
- Shihoko Komine‑Aizawa
- Yoichi Katayama
- Atsuo Yoshino
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Affiliations: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173‑8610, Japan, Division of Anatomical Science, Department of Functional Morphology, Nihon University School of Medicine, Tokyo 173‑8610, Japan, Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173‑8610, Japan, Division of Biomedical Sciences, Department of Physiology, Nihon University School of Medicine, Tokyo 173‑8610, Japan
Published online on: October 7, 2022 https://doi.org/10.3892/ol.2022.13541
Article Number: 421
Copyright: © Tatsuoka et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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