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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Targeting Redox Homeostasis with Arvanil Is Preferentially Cytotoxic to Glioma Stem Cells

  • Kazuki Nakamura1,2
  • Senri Takenouchi1
  • Yurika Nakagawa-Saito1
  • Yasufumi Ito1,3
  • Yuta Mitobe1,2
  • Shuhei Suzuki1,4
  • Keita Togashi1,5
  • Asuka Sugai1
  • Yukihiko Sonoda2
  • Chifumi Kitanaka1
  • Masashi Okada1
5 affiliations
  1. 1Department of Molecular Cancer Science, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan
  2. 2Department of Neurosurgery, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan
  3. 3Department of Obstetrics and Gynecology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan
  4. 4Department of Clinical Oncology, Yamagata Prefectural Shinjo Hospital, 720-1 Kanazawa, Shinjo 996-8585, Japan
  5. 5Department of Ophthalmology and Visual Sciences, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan
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Abstract

Glioma stem cells (GSCs) are cancer stem cells in glioblastoma (GBM) that are resistant to both radiotherapy and chemotherapy and contribute to tumor recurrence. Therefore, the development of GSC-targeted therapies is urgently needed to improve the poor prognosis of GBM patients. Given the growing interest in redox homeostasis, which is closely linked to mitochondrial metabolism supporting the unique properties of GSCs, we focused on capsaicin, a widely used exogenous calcium channel agonist, and its structural analogs as candidate compounds capable of disrupting redox homeostasis in GSCs. Based on a comprehensive evaluation of the effects of the candidate compounds, we found that the capsaicin analog arvanil selectively induced cell death in GSCs with high selectivity over differentiated GSCs at concentrations that were non-toxic to normal cells. Arvanil-induced cell death was associated with a preferential elevation in intracellular reactive oxygen species (ROS) levels in GSCs over those in differentiated GSCs and was suppressed by a Ca2+ chelator and a mitochondria-targeted antioxidant. These results suggest that arvanil preferentially induced GSC death in association with intracellular Ca2+ dysregulation and mitochondria-related oxidative stress, highlighting potential vulnerabilities in the redox homeostasis of GSCs and supporting further investigations on arvanil as a feasible therapeutic approach for GBM.

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Cite

BibTeXRIS
BibTeX
@article{nakamura2026targeting,
  title = {{Targeting Redox Homeostasis with Arvanil Is Preferentially Cytotoxic to Glioma Stem Cells}},
  author = {Kazuki Nakamura and Senri Takenouchi and Yurika Nakagawa-Saito and Yasufumi Ito and Yuta Mitobe and Shuhei Suzuki and Keita Togashi and Asuka Sugai and Yukihiko Sonoda and Chifumi Kitanaka and Masashi Okada},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27209358},
  url = {https://www.mdpi.com/1422-0067/27/20/9358},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Targeting Redox Homeostasis with Arvanil Is Preferentially Cytotoxic to Glioma Stem Cells
AU  - Kazuki Nakamura
AU  - Senri Takenouchi
AU  - Yurika Nakagawa-Saito
AU  - Yasufumi Ito
AU  - Yuta Mitobe
AU  - Shuhei Suzuki
AU  - Keita Togashi
AU  - Asuka Sugai
AU  - Yukihiko Sonoda
AU  - Chifumi Kitanaka
AU  - Masashi Okada
PY  - 2026
DA  - 2026/10/01
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27209358
UR  - https://www.mdpi.com/1422-0067/27/20/9358
AB  - Glioma stem cells (GSCs) are cancer stem cells in glioblastoma (GBM) that are resistant to both radiotherapy and chemotherapy and contribute to tumor recurrence. Therefore, the development of GSC-targeted therapies is urgently needed to improve the poor prognosis of GBM patients. Given the growing interest in redox homeostasis, which is closely linked to mitochondrial metabolism supporting the unique properties of GSCs, we focused on capsaicin, a widely used exogenous calcium channel agonist, and its structural analogs as candidate compounds capable of disrupting redox homeostasis in GSCs. Based on a comprehensive evaluation of the effects of the candidate compounds, we found that the capsaicin analog arvanil selectively induced cell death in GSCs with high selectivity over differentiated GSCs at concentrations that were non-toxic to normal cells. Arvanil-induced cell death was associated with a preferential elevation in intracellular reactive oxygen species (ROS) levels in GSCs over those in differentiated GSCs and was suppressed by a Ca2+ chelator and a mitochondria-targeted antioxidant. These results suggest that arvanil preferentially induced GSC death in association with intracellular Ca2+ dysregulation and mitochondria-related oxidative stress, highlighting potential vulnerabilities in the redox homeostasis of GSCs and supporting further investigations on arvanil as a feasible therapeutic approach for GBM.
SN  - 1422-0067
ER  -