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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.

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Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, Thailand.
Division of Anatomy, Department of Preclinical Science, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand.
Prasat Neurological Institute, Bangkok, Thailand.
Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.


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.


Gelatinase; Glioma; Invasion; Migration; Montelukast; Zafirlukast

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