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

Document Type: Research Articles

Authors

Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.

Abstract

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, MDAMB-
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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