Promoting oligodendroglial-oriented differentiation of glioma stem cell: a repurposing of quetiapine for the treatment of malignant glioma

Oncotarget. 2017 Jun 6;8(23):37511-37524. doi: 10.18632/oncotarget.16400.


As a major contributor of chemotherapy resistance and malignant recurrence, glioma stem cells (GSCs) have been proposed as a target for the treatment of gliomas. To evaluate the therapeutic potential of quetiapine (QUE), an atypical antipsychotic, for the treatment of malignant glioma, we established mouse models with GSCs-initiated orthotopic xenograft gliomas and subcutaneous xenograft tumors, using GSCs purified from glioblastoma cell line GL261. We investigated antitumor effects of QUE on xenograft gliomas and its underlying mechanisms on GSCs. Our data demonstrated that (i) QUE monotherapy can effectively suppress GSCs-initiated tumor growth; (ii) QUE has synergistic effects with temozolomide (TMZ) on glioma suppression, and importantly, QUE can effectively suppress TMZ-resistant (or -escaped) tumors generated from GSCs; (iii) mechanistically, the anti-glioma effect of QUE was due to its actions of promoting the differentiation of GSCs into oligodendrocyte (OL)-like cells and its inhibitory effect on the Wnt/β-catenin signaling pathway. Together, our findings suggest an effective approach for anti-gliomagenic treatment via targeting OL-oriented differentiation of GSCs. This also opens a door for repurposing QUE, an FDA approved drug, for the treatment of malignant glioma.

Keywords: Wnt/β-catenin signaling pathway; differentiation; glioma stem cell; proliferation; quetiapine.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Cell Differentiation / drug effects*
  • Cell Line, Tumor
  • Dacarbazine / administration & dosage
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / pharmacology
  • Drug Repositioning
  • Drug Synergism
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Mice, Inbred C57BL
  • Mice, Nude
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / pathology
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology
  • Oligodendroglia / pathology
  • Quetiapine Fumarate / administration & dosage
  • Quetiapine Fumarate / pharmacology*
  • Temozolomide
  • Tumor Burden / drug effects


  • Quetiapine Fumarate
  • Dacarbazine
  • Temozolomide