Montelukast, a cysteinyl leukotriene receptor antagonist, inhibits the growth of chronic myeloid leukemia cells through apoptosis

Oncology Reports
Ana ZovkoLeif Stenke

Abstract

The clinical outcome for patients with chronic myeloid leukemia (CML) has improved significantly with the introduction of tyrosine kinase inhibitors (TKIs). However, their curative potential appears limited, probably as a consequence of TKI-resistant leukemic stem cells (LSCs) that persist as a result of aberrant pathways independent of the well-established oncoprotein Bcr-Abl. One such pathway involves signaling through leukotrienes (LTs), bioactive compounds that have been suggested to play a role in several other malignancies. Cysteinyl LT1 receptor (CysLT1R) has been reported to be overexpressed in a number of solid cancers, and blocking of this receptor with the antagonist montelukast (treatment approved for bronchial asthma) has resulted in the killing of cancer cells. We recently demonstrated that montelukast, alone or in combination with imatinib, can effectively reduce the growth of CML cells, while normal bone marrow cells were left unaffected. Herein, we further investigated the importance of CysLT1R for the survival of CML cells and the mechanisms by which montelukast induces cell death. Knockdown of the CysLT1R of K562 cells with siRNA reduced their growth by 25%. Montelukast had no effect on these cells, while it ...Continue Reading

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