Evaluation of the effects of sertraline and penfluridol on tumorigenesis and metastatic cell behavior in human glioblastoma cells: Ddrug repositioning

Glioblastoma multiforme (Stage IV) is the most common and malignant primary neoplasm in adults. Although there are multimodal treatment approaches including surgical resection, chemotherapy, and radiotherapy, the mean survival is less than 15 months. Therefore, there is an urgent need for the identification of new FDA-approved therapeutic drugs that can be used in the treatment of glioblastoma and capable of crossing the blood-brain barrier. In this regard, the aim of our study was to investigate the effects of an antipsychotic, Penfluridol, and an antidepressant, Sertraline, on tumorigenesis and metastatic cell behavior in human glioblastoma cell lines (U87 and U251) and to reposition these drugs for the glioblastoma treatment. In this context, cell viability was first analyzed with WST-1 to determine inhibitory concentrations of Sertraline or Penfluridol (IC50) in U87 and U251 cells. Then the effects of Sertraline and Penfluridol on colony formation, spheroid proliferation and apoptosis in U87 and U251 cells were investigated by colony formation, 3D spheroid proliferation assay and flow cytometry, respectively. In these cells, wound healing, matrigel invasion, and cell adhesion assays were performed to investigate the effects of Sertraline and Penfluridol on metastatic cell behavior. When the results were examined, it was observed that both Sertraline and Penfluridol triggered cell death and significantly suppressed colony formation and spheroid proliferation. Sertraline also significantly inhibited cell migration/invasion/adhesion, on the other hand, Penfluridol had no significant effect on metastatic cell behavior. In the light of these data, we presume that Penfluridol can be used specifically anti-carcinogenic agent, whereas Sertraline has the potential to be used as not only an anti-carcinogenic but also an anti-metastatic agent for the treatment of glioblastoma. Keywords: Glioblastoma multiforme, Sertraline, Penfluridol, Apoptosis, Metastatic cell behavior