Cysteinyl leukotriene receptor antagonists induce apoptosis and inhibit proliferation of human glioblastoma cells by downregulating b-cell lymphoma 2 and inducing cell cycle arrest
© 2018, Canadian Science Publishing. All rights reserved. Glioblastoma is the most aggressive type of brain cancer with the highest proliferation, invasion, and migration. Montelukast and zafirlukast, 2 widely used leukotriene receptor antagonists (LTRAs) for asthma treatment, inhibited invasion and...
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th-mahidol.452772019-08-28T13:53:52Z Cysteinyl leukotriene receptor antagonists induce apoptosis and inhibit proliferation of human glioblastoma cells by downregulating b-cell lymphoma 2 and inducing cell cycle arrest Pannaree Piromkraipak Tipparat Parakaw Suttinee Phuagkhaopong Sirada Srihirun Sukumal Chongthammakun Kulathida Chaithirayanon Pornpun Vivithanaporn Mahidol University Biochemistry, Genetics and Molecular Biology Medicine Pharmacology, Toxicology and Pharmaceutics © 2018, Canadian Science Publishing. All rights reserved. Glioblastoma is the most aggressive type of brain cancer with the highest proliferation, invasion, and migration. Montelukast and zafirlukast, 2 widely used leukotriene receptor antagonists (LTRAs) for asthma treatment, inhibited invasion and migration of glioblastoma cell lines. Montelukast induces apoptosis and inhibits cell proliferation of various cancer cells. Herein, apoptotic and antiproliferative effects of montelukast and zafirlukast were investigated in 2 glioblastoma cell lines, A172 and U-87 MG. Both LTRAs induced apoptosis and inhibited cell proliferation of glioblastoma cells in a concentration-dependent manner. Montelukast was more cytotoxic and induced higher levels of apoptosis than zafirlukast in A172 cells, but not in U-87 MG cells. Both drugs decreased expression of B-cell lymphoma 2 (Bcl-2) protein without affecting Bcl-2-associated X (Bax) levels. LTRAs also reduced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). In contrast, zafirlukast showed a greater antiproliferative effect than montelukast and induced G0/G1 cell cycle arrest by upregulating p53 and p21 expression. These results suggested the therapeutic potential of LTRAs in glioblastoma. 2019-08-23T10:38:40Z 2019-08-23T10:38:40Z 2018-01-01 Article Canadian Journal of Physiology and Pharmacology. Vol.96, No.8 (2018), 798-806 10.1139/cjpp-2017-0757 12057541 00084212 2-s2.0-85050941403 https://repository.li.mahidol.ac.th/handle/123456789/45277 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85050941403&origin=inward |
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Biochemistry, Genetics and Molecular Biology Medicine Pharmacology, Toxicology and Pharmaceutics Pannaree Piromkraipak Tipparat Parakaw Suttinee Phuagkhaopong Sirada Srihirun Sukumal Chongthammakun Kulathida Chaithirayanon Pornpun Vivithanaporn Cysteinyl leukotriene receptor antagonists induce apoptosis and inhibit proliferation of human glioblastoma cells by downregulating b-cell lymphoma 2 and inducing cell cycle arrest |
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© 2018, Canadian Science Publishing. All rights reserved. Glioblastoma is the most aggressive type of brain cancer with the highest proliferation, invasion, and migration. Montelukast and zafirlukast, 2 widely used leukotriene receptor antagonists (LTRAs) for asthma treatment, inhibited invasion and migration of glioblastoma cell lines. Montelukast induces apoptosis and inhibits cell proliferation of various cancer cells. Herein, apoptotic and antiproliferative effects of montelukast and zafirlukast were investigated in 2 glioblastoma cell lines, A172 and U-87 MG. Both LTRAs induced apoptosis and inhibited cell proliferation of glioblastoma cells in a concentration-dependent manner. Montelukast was more cytotoxic and induced higher levels of apoptosis than zafirlukast in A172 cells, but not in U-87 MG cells. Both drugs decreased expression of B-cell lymphoma 2 (Bcl-2) protein without affecting Bcl-2-associated X (Bax) levels. LTRAs also reduced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). In contrast, zafirlukast showed a greater antiproliferative effect than montelukast and induced G0/G1 cell cycle arrest by upregulating p53 and p21 expression. These results suggested the therapeutic potential of LTRAs in glioblastoma. |
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Mahidol University |
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Mahidol University Pannaree Piromkraipak Tipparat Parakaw Suttinee Phuagkhaopong Sirada Srihirun Sukumal Chongthammakun Kulathida Chaithirayanon Pornpun Vivithanaporn |
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Pannaree Piromkraipak Tipparat Parakaw Suttinee Phuagkhaopong Sirada Srihirun Sukumal Chongthammakun Kulathida Chaithirayanon Pornpun Vivithanaporn |
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Pannaree Piromkraipak |
title |
Cysteinyl leukotriene receptor antagonists induce apoptosis and inhibit proliferation of human glioblastoma cells by downregulating b-cell lymphoma 2 and inducing cell cycle arrest |
title_short |
Cysteinyl leukotriene receptor antagonists induce apoptosis and inhibit proliferation of human glioblastoma cells by downregulating b-cell lymphoma 2 and inducing cell cycle arrest |
title_full |
Cysteinyl leukotriene receptor antagonists induce apoptosis and inhibit proliferation of human glioblastoma cells by downregulating b-cell lymphoma 2 and inducing cell cycle arrest |
title_fullStr |
Cysteinyl leukotriene receptor antagonists induce apoptosis and inhibit proliferation of human glioblastoma cells by downregulating b-cell lymphoma 2 and inducing cell cycle arrest |
title_full_unstemmed |
Cysteinyl leukotriene receptor antagonists induce apoptosis and inhibit proliferation of human glioblastoma cells by downregulating b-cell lymphoma 2 and inducing cell cycle arrest |
title_sort |
cysteinyl leukotriene receptor antagonists induce apoptosis and inhibit proliferation of human glioblastoma cells by downregulating b-cell lymphoma 2 and inducing cell cycle arrest |
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2019 |
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https://repository.li.mahidol.ac.th/handle/123456789/45277 |
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1763487537528045568 |