Next Article in Journal
Rapid Non-Enzymatic Glycation of the Insulin Receptor under Hyperglycemic Conditions Inhibits Insulin Binding In Vitro: Implications for Insulin Resistance
Next Article in Special Issue
Peiminine Protects Dopaminergic Neurons from Inflammation-Induced Cell Death by Inhibiting the ERK1/2 and NF-κB Signalling Pathways
Previous Article in Journal
Diffuse Axonal Injury and Oxidative Stress: A Comprehensive Review
Previous Article in Special Issue
KLF2 in Regulation of NF-κB-Mediated Immune Cell Function and Inflammation
Article Menu
Issue 12 (December) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(12), 2603; https://doi.org/10.3390/ijms18122603

Quinacrine Inhibits ICAM-1 Transcription by Blocking DNA Binding of the NF-κB Subunit p65 and Sensitizes Human Lung Adenocarcinoma A549 Cells to TNF-α and the Fas Ligand

1
Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
2
The Center for Advanced Insect Research Promotion (CAIRP), Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
*
Author to whom correspondence should be addressed.
Received: 17 November 2017 / Revised: 29 November 2017 / Accepted: 30 November 2017 / Published: 2 December 2017
(This article belongs to the Special Issue NF-κB and Cancer)
Full-Text   |   PDF [3190 KB, uploaded 2 December 2017]   |  

Abstract

Quinacrine has been used for therapeutic drugs in some clinical settings. In the present study, we demonstrated that quinacrine decreased the expression of intercellular adhesion molecule-1 (ICAM-1) induced by tumor necrosis factor (TNF)-α and interleukin-1 (IL-1) α in human lung adenocarcinoma A549 cells. Quinacrine inhibited ICAM-1 mRNA expression and nuclear factor κB (NF-κB)-responsive luciferase reporter activity following a treatment with TNF-α and IL-1α. In the NF-κB signaling pathway, quinacrine did not markedly affect the TNF-α-induced degradation of the inhibitor of NF-κB or the TNF-α-induced phosphorylation of the NF-κB subunit, p65, at Ser-536 and its subsequent translocation to the nucleus. In contrast, a chromatin immunoprecipitation assay showed that quinacrine prevented the binding of p65 to the ICAM-1 promoter following TNF-α stimulation. Moreover, TNF-α and the Fas ligand effectively reduced the viability of A549 cells in the presence of quinacrine only. Quinacrine down-regulated the constitutive and TNF-α-induced expression of c-FLIP and Mcl-1 in A549 cells. These results revealed that quinacrine inhibits ICAM-1 transcription by blocking the DNA binding of p65 and sensitizes A549 cells to TNF-α and the Fas ligand. View Full-Text
Keywords: quinacrine; nuclear factor κB (NF-κB); tumor necrosis-α (TNF-α); intercellular adhesion molecule-1 (ICAM-1); the Fas ligand quinacrine; nuclear factor κB (NF-κB); tumor necrosis-α (TNF-α); intercellular adhesion molecule-1 (ICAM-1); the Fas ligand
Figures

Figure 1

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).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Harada, M.; Morimoto, K.; Kondo, T.; Hiramatsu, R.; Okina, Y.; Muko, R.; Matsuda, I.; Kataoka, T. Quinacrine Inhibits ICAM-1 Transcription by Blocking DNA Binding of the NF-κB Subunit p65 and Sensitizes Human Lung Adenocarcinoma A549 Cells to TNF-α and the Fas Ligand. Int. J. Mol. Sci. 2017, 18, 2603.

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