Repurposing Penfluridol in combination with temozolomide for the treatment of glioblastoma

Hyungsin Kim, Kyuha Chong, Byung Kyu Ryu, Kyung Jae Park, Mi Ok Yu, Jihye Lee, Seok Chung, Seongkyun Choi, Myung Jin Park, Yong Gu Chung, Shin Hyuk Kang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Despite the presence of aggressive treatment strategies, glioblastoma remains intractable, warranting a novel therapeutic modality. An oral antipsychotic agent, penflurido (PFD), used for schizophrenia treatment, has shown an antitumor effect on various types of cancer cells. As glioma sphere-forming cells (GSCs) are known to mediate drug resistance in glioblastoma, and considering that antipsychotics can easily penetrate the blood-brain barrier, we investigated the antitumor effect of PFD on patient-derived GSCs. Using five GSCs, we found that PFD exerts an antiproliferative effect in a time- and dose-dependent manner. At IC50, spheroid size and second-generation spheroid formation were significantly suppressed. Stemness factors, SOX2 and OCT4, were decreased. PFD treatment reduced cancer cell migration and invasion by reducing the Integrin α6 and uPAR levels and suppression of the expression of epithelial-to-mesenchymal transition (EMT) factors, vimentin and Zeb1. GLI1 was found to be involved in PFD-induced EMT inhibition. Furthermore, combinatorial treatment of PFD with temozolomide (TMZ) significantly suppressed tumor growth and prolonged survival in vivo. Immunostaining revealed decreased expression of GLI1, SOX2, and vimentin in the PFD treatment group but not in the TMZ-only treatment group. Therefore, PFD can be effectively repurposed for the treatment of glioblastoma by combining it with TMZ.

Original languageEnglish
Article number1310
JournalCancers
Volume11
Issue number9
DOIs
Publication statusPublished - 2019 Sep

Keywords

  • Glioblastom
  • Penfluridol
  • Sphere forming cell
  • Temozolomide
  • Tumor growth

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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