Next Article in Journal
Hypotheses on the Potential of Rice Bran Intake to Prevent Gastrointestinal Cancer through the Modulation of Oxidative Stress
Next Article in Special Issue
The between Now and Then of Lung Cancer Chemotherapy and Immunotherapy
Previous Article in Journal
MicroRNA-210 Suppresses Junction Proteins and Disrupts Blood-Brain Barrier Integrity in Neonatal Rat Hypoxic-Ischemic Brain Injury
Previous Article in Special Issue
Novel Structurally Related Flavones Augment Cell Death Induced by rhsTRAIL
Article Menu
Issue 7 (July) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(7), 1353; doi:10.3390/ijms18071353

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

1
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
2
Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
3
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
4
Department of Respiratory Therapy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
5
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
6
Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
*
Authors to whom correspondence should be addressed.
Received: 11 May 2017 / Revised: 19 June 2017 / Accepted: 21 June 2017 / Published: 24 June 2017
(This article belongs to the Special Issue Tumor Targeting Therapy and Selective Killing)
View Full-Text   |   Download PDF [5099 KB, uploaded 27 June 2017]   |  

Abstract

Developing novel chemo-prevention techniques and advancing treatment are key elements to beating lung cancer, the most common cause of cancer mortality worldwide. Our previous cohort study showed that cysteinyl leukotriene receptor antagonists, mainly montelukast, decreased the lung cancer risk in asthma patients. In the current study, we conducted in vivo and in vitro experiments to demonstrate the inhibiting effect of montelukast on lung cancer and to investigate the underlying mechanisms. Using Lewis lung carcinoma-bearing mice, we showed that feeding montelukast significantly delayed the tumor growth in mice (p < 0.0001). Montelukast inhibited cell proliferation and colony formation and induced the cell death of lung cancer cells. Further investigation showed the down-regulation of B-cell lymphoma 2 (Bcl-2), up-regulation of Bcl-2 homologous antagonist/killer (Bak), and nuclear translocation of apoptosis-inducing factor (AIF) in montelukast-treated lung cancer cells. Montelukast also markedly decreased the phosphorylation of several proteins, such as with no lysine 1 (WNK1), protein kinase B (Akt), extracellular signal-regulated kinase 1/2 (Erk1/2), MAPK/Erk kinase (MEK), and proline-rich Akt substrate of 40-kDa (PRAS40), which might contribute to cell death. In conclusion, montelukast induced lung cancer cell death via the nuclear translocation of AIF. This study confirmed the chemo-preventive effect of montelukast shown in our previous cohort study. The utility of montelukast in cancer prevention and treatment thus deserves further studies. View Full-Text
Keywords: cysteinyl leukotriene receptor antagonists; montelukast; lung cancer; apoptosis-inducing factor; asthma cysteinyl leukotriene receptor antagonists; montelukast; lung cancer; apoptosis-inducing factor; asthma
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Tsai, M.-J.; Chang, W.-A.; Tsai, P.-H.; Wu, C.-Y.; Ho, Y.-W.; Yen, M.-C.; Lin, Y.-S.; Kuo, P.-L.; Hsu, Y.-L. Montelukast Induces Apoptosis-Inducing Factor-Mediated Cell Death of Lung Cancer Cells. Int. J. Mol. Sci. 2017, 18, 1353.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top