Format

Send to

Choose Destination
J Neurooncol. 2019 Jan;141(2):267-276. doi: 10.1007/s11060-018-03040-8. Epub 2018 Nov 9.

Magmas inhibition as a potential treatment strategy in malignant glioma.

Di K1, Lomeli N2, Bota DA3,4,5,6,7, Das BC8.

Author information

1
Department of Neurology, University of California Irvine, Irvine, CA, USA.
2
Department of Pathology & Laboratory Medicine, University of California Irvine, Irvine, CA, USA.
3
Department of Neurology, University of California Irvine, Irvine, CA, USA. dbota@uci.edu.
4
Department of Pathology & Laboratory Medicine, University of California Irvine, Irvine, CA, USA. dbota@uci.edu.
5
Department of Neurological Surgery, University of California Irvine, Irvine, CA, USA. dbota@uci.edu.
6
Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA. dbota@uci.edu.
7
, 200 S. Manchester Ave., Suite 206, Orange, CA, 92868, USA. dbota@uci.edu.
8
Department of Medicine and Pharmacological Sciences, The Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. Bhaskar.das@mssm.edu.

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.

KEYWORDS:

Anti-tumor activity; Glioma; Magmas; ROS; Small molecule inhibitor

PMID:
30414099
PMCID:
PMC6474352
DOI:
10.1007/s11060-018-03040-8
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center