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Leukotriene Receptor Antagonists Inhibit Mitogenic Activity in Triple Negative Breast Cancer Cells

Despite a discovery of hormonal pathways regulating breast cancer, a definitive cure for the disease requires further identification of alternative targets that provide a hormone-independent support. Apart from their role in inflammatory diseases, cysteinyl leukotriene (CysLT) receptor antagonists (...

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Autores principales: Suknuntha, Kran, Yubolphan, Ruedeemars, Krueaprasertkul, Kanokpan, Srihirun, Sirada, Sibmooh, Nathawut, Vivithanaporn, Pornpun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: West Asia Organization for Cancer Prevention 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980863/
https://www.ncbi.nlm.nih.gov/pubmed/29582642
http://dx.doi.org/10.22034/APJCP.2018.19.3.833
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author Suknuntha, Kran
Yubolphan, Ruedeemars
Krueaprasertkul, Kanokpan
Srihirun, Sirada
Sibmooh, Nathawut
Vivithanaporn, Pornpun
author_facet Suknuntha, Kran
Yubolphan, Ruedeemars
Krueaprasertkul, Kanokpan
Srihirun, Sirada
Sibmooh, Nathawut
Vivithanaporn, Pornpun
author_sort Suknuntha, Kran
collection PubMed
description Despite a discovery of hormonal pathways regulating breast cancer, a definitive cure for the disease requires further identification of alternative targets that provide a hormone-independent support. Apart from their role in inflammatory diseases, cysteinyl leukotriene (CysLT) receptor antagonists (LTRAs) decrease the risk of lung cancer in asthma patients and inhibit tumor progression in several malignancies. In the present study, we evaluate the effects of two chemically different, clinically relevant LTRAs (montelukast and zafirlukast) in a triple negative breast cancer cell line, MDA-MB-231. We found that these two LTRAs reduced breast cancer cell viability in a dose-dependent manner with the 50% inhibitory concentration (IC50) between 5-10 μM. Although both LTRAs have several pharmacological properties in common, we noticed that montelukast mainly induced apoptosis, while zafirlukast mainly exerted its action on cell cycle. However, the precise mechanisms responsible for such different effects remain unclear. In summary, our results suggest that CysLT plays a role in proliferation and survivability of breast cancer cells in the absence of hormonal stimuli.
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spelling pubmed-59808632018-06-06 Leukotriene Receptor Antagonists Inhibit Mitogenic Activity in Triple Negative Breast Cancer Cells Suknuntha, Kran Yubolphan, Ruedeemars Krueaprasertkul, Kanokpan Srihirun, Sirada Sibmooh, Nathawut Vivithanaporn, Pornpun Asian Pac J Cancer Prev Research Article Despite a discovery of hormonal pathways regulating breast cancer, a definitive cure for the disease requires further identification of alternative targets that provide a hormone-independent support. Apart from their role in inflammatory diseases, cysteinyl leukotriene (CysLT) receptor antagonists (LTRAs) decrease the risk of lung cancer in asthma patients and inhibit tumor progression in several malignancies. In the present study, we evaluate the effects of two chemically different, clinically relevant LTRAs (montelukast and zafirlukast) in a triple negative breast cancer cell line, MDA-MB-231. We found that these two LTRAs reduced breast cancer cell viability in a dose-dependent manner with the 50% inhibitory concentration (IC50) between 5-10 μM. Although both LTRAs have several pharmacological properties in common, we noticed that montelukast mainly induced apoptosis, while zafirlukast mainly exerted its action on cell cycle. However, the precise mechanisms responsible for such different effects remain unclear. In summary, our results suggest that CysLT plays a role in proliferation and survivability of breast cancer cells in the absence of hormonal stimuli. West Asia Organization for Cancer Prevention 2018 /pmc/articles/PMC5980863/ /pubmed/29582642 http://dx.doi.org/10.22034/APJCP.2018.19.3.833 Text en Copyright: © Asian Pacific Journal of Cancer Prevention http://creativecommons.org/licenses/BY-SA/4.0 This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
spellingShingle Research Article
Suknuntha, Kran
Yubolphan, Ruedeemars
Krueaprasertkul, Kanokpan
Srihirun, Sirada
Sibmooh, Nathawut
Vivithanaporn, Pornpun
Leukotriene Receptor Antagonists Inhibit Mitogenic Activity in Triple Negative Breast Cancer Cells
title Leukotriene Receptor Antagonists Inhibit Mitogenic Activity in Triple Negative Breast Cancer Cells
title_full Leukotriene Receptor Antagonists Inhibit Mitogenic Activity in Triple Negative Breast Cancer Cells
title_fullStr Leukotriene Receptor Antagonists Inhibit Mitogenic Activity in Triple Negative Breast Cancer Cells
title_full_unstemmed Leukotriene Receptor Antagonists Inhibit Mitogenic Activity in Triple Negative Breast Cancer Cells
title_short Leukotriene Receptor Antagonists Inhibit Mitogenic Activity in Triple Negative Breast Cancer Cells
title_sort leukotriene receptor antagonists inhibit mitogenic activity in triple negative breast cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980863/
https://www.ncbi.nlm.nih.gov/pubmed/29582642
http://dx.doi.org/10.22034/APJCP.2018.19.3.833
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