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Montelukast Induces Apoptosis-Inducing Factor-Mediated Cell Death of Lung Cancer Cells

Ming-Ju Tsai1,2,3,4, Wei-An Chang5,6, Pei-Hsun Tsai7,8,9

  • 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan. SiegfriedTsai@gmail.com.

International Journal of Molecular Sciences
|July 5, 2017
PubMed

Insights

Montelukast, a cysteinyl leukotriene receptor antagonist, inhibits lung cancer growth and induces cell death by promoting apoptosis-inducing factor (AIF) nuclear translocation. This confirms its potential as a lung cancer chemo-preventive agent.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Lung cancer remains the leading cause of cancer mortality globally.
  • Cysteinyl leukotriene receptor antagonists, like montelukast, previously showed potential in reducing lung cancer risk in asthma patients.

Purpose of the Study:

  • To demonstrate the inhibitory effect of montelukast on lung cancer growth and cell death.
  • To elucidate the underlying molecular mechanisms of montelukast's anti-cancer action.

Main Methods:

  • In vivo studies using Lewis lung carcinoma-bearing mice.
  • In vitro experiments on lung cancer cell lines.
  • Analysis of apoptosis-related protein expression and signaling pathway modulation.

Main Results:

  • Montelukast significantly delayed tumor growth in mice (p < 0.0001).
  • Montelukast inhibited lung cancer cell proliferation and colony formation, inducing cell death.
  • Mechanisms involved down-regulation of Bcl-2, up-regulation of Bak, and nuclear translocation of AIF, alongside decreased phosphorylation of key signaling proteins (WNK1, Akt, Erk1/2, MEK, PRAS40).

Conclusions:

  • Montelukast induces lung cancer cell death primarily through the nuclear translocation of AIF.
  • The findings support montelukast's chemo-preventive and potential therapeutic role in lung cancer, warranting further investigation.
Keywords:
apoptosis-inducing factorasthmacysteinyl leukotriene receptor antagonistslung cancermontelukast

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