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Cancer Chemotherapy and Pharmacology

, Volume 80, Issue 2, pp 411–419 | Cite as

Hinokitiol suppresses cancer stemness and oncogenicity in glioma stem cells by Nrf2 regulation

  • Wen-Chen Ouyang
  • Yi-Wen Liao
  • Pei-Ni Chen
  • Kai-Hsi Lu
  • Cheng-Chia YuEmail author
  • Pei-Ling HsiehEmail author
Original Article

Abstract

Purpose

Glioma is one of the lethal malignancies with poor prognosis. In addition, glioma stem cells (GSCs) have been considered as the crucial player that attributed to the tumorigenesis and drug resistance. In the current study, we investigated the therapeutic effect of hinokitiol, a natural bioactive compound of aromatic tropolone, on the characteristics of GSCs and the possible mechanism.

Methods

U87MG and T98G glioma cells were used to isolate GSCs. CD133 positivity and ALDH1 activity of GSCs following hinokitiol treatment were assessed by flow cytometry analysis. Secondary sphere formation, migration, invasion, and colony-forming assays were performed to examine the self-renewal capacity and oncogenicity in GCS after hinokitiol administration. The expression of Nrf2 was evaluated by RT-PCR and western blot analyses.

Results

We demonstrated that hinokitiol effectively inhibited the CD133 positivity and ALDH1 activity along with the reduced self-renewal, migration, invasion, and colony formation properties of GSCs. In addition, hinokitiol repressed the gene and protein expression of Nrf2, which has been shown to be critical for those GSCs features. Furthermore, we showed that administration of exogenous Nrf2 counteracted the inhibitory effect of hinokitiol on self-renewal and invasiveness of GSCs.

Conclusion

These evidences suggest that treatment of hinokitiol significantly attenuates the hallmarks of GSCs due to downregulation of Nrf2 expression. Hence, hinokitiol may serve as a promising agent for the therapy of glioma.

Keywords

Hinokitiol Glioma stem cells Nrf2 Cancer stemness 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.

Funding

The present study was supported by Grants from the Changhua Christian Hospital and Chung Shan Medical University (CSMU-CCH-103-05) in Taiwan.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Psychiatry, Changhua Christian HospitalChanghua Christian Healthcare SystemChanghuaTaiwan
  2. 2.Section of PsychiatryLutung Christian HospitalChanghuaTaiwan
  3. 3.Department of Psychiatry, Kaohsiung Chung-Ho Memorial HospitalKaohsiung Medical UniversityKaohsiungTaiwan
  4. 4.School of DentistryChung Shan Medical UniversityTaichungTaiwan
  5. 5.Institute of Biochemistry, Microbiology and ImmunologyChung Shan Medical UniversityTaichungTaiwan
  6. 6.Department of Medical Research and EducationCheng-Hsin General HospitalTaipeiTaiwan
  7. 7.Institute of Oral SciencesChung Shan Medical UniversityTaichungTaiwan
  8. 8.Department of DentistryChung Shan Medical University HospitalTaichungTaiwan

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