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Magmas inhibition as a potential treatment strategy in malignant glioma

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Purpose

Magmas (mitochondria-associated protein involved in granulocyte–macrophage colony-stimulating factor signal transduction) is a nuclear gene that encodes the mitochondrial import inner membrane translocase subunit Tim16. Magmas is highly conserved, ubiquitously expressed in mammalian cells, and is essential for cell viability. Magmas expression levels are increased in prostate cancers and pituitary adenomas. Moreover, silencing Magmas by RNAi sensitizes pituitary adenoma cells to pro-apoptotic stimuli and induces a G0/G1 accumulation. The aim of this study was to examine whether inhibition of Magmas by small molecule inhibitors could be beneficial for the treatment of malignant gliomas.

Methods

We evaluated the expression of Magmas in patient-derived glioblastoma tissue samples and xenograft models. We studied the feasibility of a small molecule Magmas inhibitor (BT#9) as a therapeutic agent in stable human glioma cell lines and high-grade patient derived glioma stem-like cells.

Results

Magmas was overexpressed in tissue sections from glioma patients and xenografts. In vivo studies revealed that BT#9 could cross the blood–brain barrier in the animal model. Magmas inhibition by BT#9 in glioma cell lines significantly decreased cell proliferation, induced apoptosis along with vacuole formation, and blocked migration and invasion. In addition, BT#9 treatment decreased the respiratory function of glioma cells, supporting the role that Magmas serves as a reactive oxygen species regulator.

Conclusions

This is the first study on the role of Magmas in glioma. Our findings suggest that Magmas plays a key role in glioma cell survival and targeting Magmas by small molecule inhibitors may be a therapeutic strategy in gliomas.

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Acknowledgements

This study was supported by donations from grateful patients to Dr. Bota laboratory and the UCI Cancer Center Award Number P30CA062203 from the National Cancer Institute (NCI/NIH). Dr. Das is thankful to Dr. Michael Baltezor (Director, Biotechnology Innovation and Optimization Center, Kansas City, KS) for the PK studies.

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Authors and Affiliations

  1. Department of Neurology, University of California Irvine, Irvine, CA, USA

    Kaijun Di & Daniela A. Bota

  2. Department of Pathology & Laboratory Medicine, University of California Irvine, Irvine, CA, USA

    Naomi Lomeli & Daniela A. Bota

  3. Department of Neurological Surgery, University of California Irvine, Irvine, CA, USA

    Daniela A. Bota

  4. Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA

    Daniela A. Bota

  5. Department of Medicine and Pharmacological Sciences, The Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Bhaskar C. Das

  6. 200 S. Manchester Ave., Suite 206, Orange, CA, 92868, USA

    Daniela A. Bota

Authors
  1. Kaijun Di
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  2. Naomi Lomeli
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  3. Daniela A. Bota
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  4. Bhaskar C. Das
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Corresponding authors

Correspondence to Daniela A. Bota or Bhaskar C. Das.

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The authors declare no potential conflict of interests.

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Di, K., Lomeli, N., Bota, D.A. et al. Magmas inhibition as a potential treatment strategy in malignant glioma. J Neurooncol 141, 267–276 (2019). https://doi.org/10.1007/s11060-018-03040-8

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  • DOI: https://doi.org/10.1007/s11060-018-03040-8

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