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PO1-8-5

Montelukast Induces Apoptosis and Inhibits Proliferation of Human Glioblastoma Cells by Decreasing B-cell Lymphoma 2 Expression

[Speaker] Pornpun Vivithanaporn:1
[Co-author] Pannaree Piromkraipak:1, Tipparat Parakaw:2, Suttinee Phaugkhaopong:1
1:Department of Pharmacology, Faculty of Science, Mahidol University, Thailand, 2:Department of Pharmacology, Faculty of Dentistry, Mahidol University, Thailand

Background: A large epidemiological study in asthmatic patients showed that montelukast, a leukotriene receptor antagonist, lower the risk of several types of cancers. Montelukast inhibited invasion and migration of glioblastoma cell lines. Montelukast induced apoptosis of lung, renal, colon, prostate and testicular cancers. The present study aim to elucidate the apoptotic and anti-proliferative effects of leukotriene antagonist.
Methods: Cell viability, apoptotic and antiproliferative effects were investigated in U-87 MG cells using MTT, Annexin V apoptosis, Western blotting and CFSE proliferation assays, respectively.
Results: Montelukast at 10 μM reduced cell viability of U-87 MG cells about 50% while 20 μM decreased cell viability to less than 10% at 24 hours. Montelukast at 20 μM induced early and late apoptosis as indicated by increased numbers of Annexin V-FITC positive/7-aminoactinomycin D (7-AAD) negative cells and Annexin V-FITC positive/7-AAD positive cells, respectively. Moreover, 20 μM montelukast reduced the expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein. In addition to apoptotic effect, 20 μM montelukast increased the mean fluorescence intensity of CFSE staining at day 4 post-exposure.
Conclusion: These results suggested that inhibition of cysteinyl leukotriene receptor type 1 triggers apoptosis and down-regulates proliferation of glioblastoma cells.

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