Escitalopram oxalate induces apoptosis in U-87MG cells and autophagy in GBM8401 cells.

Vincent Chin‐Hung Chen,Tsai‐Ching Hsu,Bor‐Show Tzang,Yi‐Hsien Hsieh,Li‐Jeng Chen

doi:10.1111/jcmm.13372

Abstract

Glioblastoma multiforme (GBM) is recognized as a most aggressive brain cancer with the worst prognosis and survival time. Owing to the anatomic location of gliomas, surgically removing the tumour is very difficult and avoiding damage to vital brain regions during radiotherapy is impossible. Therefore, therapeutic strategies for malignant glioma must urgently be improved. Recent studies have demonstrated that selective serotonin reuptake inhibitors (SSRIs) have cytotoxic effect on certain cancers. Considering as a more superior SSRI, escitalopram oxalate exhibits favourable tolerability and causes generally mild and temporary adverse events. However, limited information is revealed about the influence of escitalopram oxalate on GBM. Therefore, an attempt was made herein to explore the effects of escitalopram oxalate on GBM. The experimental results revealed that escitalopram oxalate significantly inhibits the proliferation and invasive ability of U‐87MG cells and significantly reduced the expressions of cell cycle inhibitors such as Skp2, P57, P21 and P27. Notably, escitalopram oxalate also induced significant apoptotic cascades in U‐87MG cells and autophagy in GBM8401 cells. An animal study indicated that escitalopram oxalate inhibits the proliferation of xenografted glioblastoma in BALB/c nude mice. These findings implied that escitalopram oxalate may have potential in treatment of glioblastomas.

Highlights

Malignant gliomas are known as the most common brain tumours
To determine whether escitalopram oxalate induces cell death in U87MG cells, immunoblotting was performed to detect the expressions of various apoptotic proteins, including Bax, cytochrome c, Apaf-1, caspase-3, caspase-9 and PARP
The expressions of Bax, cytochrome c, Apaf-1, caspase-3, caspase-9 and PARP were significantly increased in U-87MG cells with the concentration of escitalopram oxalate (Fig. 4A)

Summary

Introduction

Malignant gliomas are known as the most common brain tumours. Gliomas are classified into four grades (Grades I–IV) according to histology and prognosis [1]. GBM is a grade IV astrocytoma and the most aggressive brain cancer with the execrable prognosis and survival rate [2, 3]. The ordinary consideration for GBM treatment is surgical resection in combination with radiotherapy and chemotherapy. The anatomic location of gliomas makes surgically removing the tumour very difficult and avoiding damage to vital brain regions during radiotherapy is impossible. Even though temozolomide chemotherapy and radiotherapy are combined with surgical resection, the average survival time in patients with grade IV glioma is nearly one and half year [4]. The alternative strategy for treatment of malignant glioma must be earnestly improved

Methods

Results

Conclusion