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

Abstract

Despite a discovery of hormonal pathways regulating breast cancer, a definitive cure for the disease requires further<br />identification of alternative targets that provide a hormone-independent support. Apart from their role in inflammatory<br />diseases, cysteinyl leukotriene (CysLT) receptor antagonists (LTRAs) decrease the risk of lung cancer in asthma patients<br />and inhibit tumor progression in several malignancies. In the present study, we evaluate the effects of two chemically<br />different, clinically relevant LTRAs (montelukast and zafirlukast) in a triple negative breast cancer cell line, MDAMB-<br />231. We found that these two LTRAs reduced breast cancer cell viability in a dose-dependent manner with the<br />50% inhibitory concentration (IC50) between 5-10 μM. Although both LTRAs have several pharmacological properties<br />in common, we noticed that montelukast mainly induced apoptosis, while zafirlukast mainly exerted its action on cell<br />cycle. However, the precise mechanisms responsible for such different effects remain unclear. In summary, our results<br />suggest that CysLT plays a role in proliferation and survivability of breast cancer cells in the absence of hormonal stimuli.