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Cell Mol Neurobiol. 2018 Mar;38(2):559-573. doi: 10.1007/s10571-017-0507-z. Epub 2017 Jun 9.

Cysteinyl Leukotriene Receptor Antagonists Inhibit Migration, Invasion, and Expression of MMP-2/9 in Human Glioblastoma.

Author information

1
Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
2
Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, Thailand.
3
Division of Anatomy, Department of Preclinical Science, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand.
4
Prasat Neurological Institute, Bangkok, Thailand.
5
Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
6
Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand. pornpun.viv@mahidol.ac.th.

Abstract

Glioblastoma is one of the most malignant and aggressive types of brain tumors. 5-lipoxygenase and cysteinyl leukotriene receptor 1 (CysLT1) play a role in human carcinogenesis. Leukotriene receptor antagonists (LTRAs), anti-asthmatic drugs with mild side effects, have anti-metastatic activity in epidermoid carcinoma, lung carcinoma, and colon cancers as well as neuroprotective effects. Herein, anti-migratory effects of two LTRAs, montelukast and zafirlukast, were investigated in glioblastoma cells. The level of CysLT1 in A172 cells was increased by 3.13 folds after IL-1β treatment. The median toxic concentration of LTRAs in A172, U373, and primary astrocytes ranged from 7.17 to 26.28 μM at 24-h post-exposure. Both LTRAs inhibited migration and invasion of glioma. Additionally, both drugs significantly inhibited the expression and activities of MMP-2 and MMP-9 in A172 and U373 glioblastoma cells and primary human astrocytes, suggesting that CysLT1 plays a role in migration and invasion of glioma, and LTRAs are potential drugs to reduce migration and invasion.

KEYWORDS:

Gelatinase; Glioma; Invasion; Migration; Montelukast; Zafirlukast

PMID:
28600709
DOI:
10.1007/s10571-017-0507-z
[Indexed for MEDLINE]

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