Thromboxane synthase suppression induces lung cancer cell apoptosis via inhibiting NF-κB

Kin Chung Leung; Ming-Yue Li; Billy C S Leung; Michael K Y Hsin; Tony S K Mok; Malcolm J Underwood; George G Chen

doi:10.1016/j.yexcr.2010.07.003

Thromboxane synthase suppression induces lung cancer cell apoptosis via inhibiting NF-κB

Exp Cell Res. 2010 Dec 10;316(20):3468-77. doi: 10.1016/j.yexcr.2010.07.003. Epub 2010 Jul 17.

Authors

Kin Chung Leung¹, Ming-Yue Li, Billy C S Leung, Michael K Y Hsin, Tony S K Mok, Malcolm J Underwood, George G Chen

Affiliation

¹ Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.

PMID: 20647010
DOI: 10.1016/j.yexcr.2010.07.003

Abstract

Accumulating evidence shows that the inhibition of thromboxane synthase (TXS) induced apoptosis in cancer cells. TXS inhibitor 1-Benzylimidzole (1-BI) can trigger apoptosis in lung cancer cells but the mechanism is not fully defined. In this study, lung cancer cells were treated with 1-BI. In this study, the level of reactive oxygen species (ROS) was measured and NF-κB activity was determined in human lung cancer cells. The roles of ROS and NF-κB in 1-BI-mediated cell death were analyzed. The results showed that 1-BI induced ROS generation but decreased the activity of NF-κB by reducing phosphorylated IκBα (p-IκBα) and inhibiting the translocation of p65 into the nucleus. In contrast to 1-BI, antioxidant N-acetyl cysteine (NAC) stimulated cell proliferation and significantly protected the cells from 1-BI-mediated cell death by neutralizing ROS. Collectively, apoptosis induced by 1-BI is associated with the over-production of ROS and the reduction of NF-κB. Antioxidants can significantly block the inhibitory effect of 1-BI.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcysteine / pharmacology
Active Transport, Cell Nucleus / drug effects
Antioxidants / pharmacology
Apoptosis / drug effects*
Caspase 3 / metabolism
Caspase 9 / metabolism
Cell Line, Tumor / cytology
Cell Line, Tumor / drug effects
Cell Line, Tumor / metabolism
Cell Nucleus / metabolism
Cell Proliferation / drug effects
Cell Survival / drug effects
Cytosol / metabolism
Drug Synergism
Enzyme Inhibitors / pharmacology
Humans
I-kappa B Proteins / metabolism
Imidazoles / pharmacology
Lung Neoplasms / metabolism
Lung Neoplasms / pathology*
Membrane Potential, Mitochondrial / drug effects
NF-KappaB Inhibitor alpha
NF-kappa B / antagonists & inhibitors*
NF-kappa B / metabolism
Nitriles / pharmacology
Phosphorylation / drug effects
Poly(ADP-ribose) Polymerases / metabolism
Reactive Oxygen Species / metabolism
Sulfones / pharmacology
Thromboxane-A Synthase / antagonists & inhibitors*
Thromboxane-A Synthase / metabolism
Transcription Factor RelA / metabolism
Tumor Necrosis Factor-alpha / pharmacology

Substances

Antioxidants
BAY 11-7085
Enzyme Inhibitors
I-kappa B Proteins
Imidazoles
NF-kappa B
NFKBIA protein, human
Nitriles
Reactive Oxygen Species
Sulfones
Transcription Factor RelA
Tumor Necrosis Factor-alpha
NF-KappaB Inhibitor alpha
1-benzylimidazole
Poly(ADP-ribose) Polymerases
Caspase 3
Caspase 9
Thromboxane-A Synthase
Acetylcysteine