Cysteinyl Leukotriene Receptor Antagonists Inhibit Migration,Invasion, and Expression of MMP-2/9 in Human Glioblastoma |
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| Authors: | Pannaree Piromkraipak Kant Sangpairoj Wuttipong Tirakotai Kulathida Chaithirayanon Supeenun Unchern Porntip Supavilai Christopher Power Pornpun Vivithanaporn |
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| Institution: | 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,Canada |
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| 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. |
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