Related Experiment Video

Updated: Mar 7, 2026

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing
09:02

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing

Published on: June 9, 2017

24.6K

Nrf2 mediates redox adaptation in NOX4-overexpressed non-small cell lung cancer cells

Qipeng Wu1, Bei Yao1, Ning Li1

  • 1Department of Clinical Pharmacy, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.

Experimental Cell Research
|February 16, 2017
PubMed

Insights

NADPH oxidase 4 (NOX4) confers apoptosis resistance in non-small cell lung cancer (NSCLC) by stabilizing nuclear factor erythroid 2-related factor 2 (Nrf2). Inhibiting Nrf2 overcomes this resistance, offering potential therapeutic targets for NSCLC.

Area of Science:

  • Cellular Biology
  • Cancer Research
  • Redox Biology

Background:

  • Redox adaptation mechanisms in cancer are complex and poorly understood.
  • NADPH oxidase 4 (NOX4) is highly expressed in non-small cell lung cancer (NSCLC) and promotes apoptosis resistance.
  • The precise mechanisms of NOX4-mediated oxidative resistance in cancer cells require further elucidation.

Purpose of the Study:

  • To investigate the comprehensive mechanisms underlying NOX4-mediated oxidative resistance in NSCLC.
  • To determine the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in NOX4-driven cancer cell adaptation.

Main Methods:

  • Studied NOX4 expression in NSCLC cells.
  • Utilized ectopic NOX4 expression and Nrf2 inhibition in A549 cells.
  • Assessed apoptosis, hydrogen peroxide (H2O2) levels, glutathione (GSH) content, and cell growth.
  • Conducted in vivo studies using xenograft tumor models.

Main Results:

  • NOX4-derived H2O2 enhanced Nrf2 stability by disrupting proteasomal degradation and increased Nrf2 activity via PI3K signaling.
  • Inhibition of Nrf2 induced apoptosis in NOX4-overexpressing A549 cells, increasing H2O2 and decreasing GSH.
  • Nrf2 inhibition suppressed cell growth and reversed NOX4-mediated growth enhancement, confirmed in vivo.

Conclusions:

  • Nrf2 plays a critical role in redox adaptation within NOX4-overexpressing NSCLC cells.
  • The NOX4-H2O2-Nrf2 axis is a key pathway for NSCLC cell survival and proliferation.
  • Targeting both NOX4 and Nrf2 simultaneously presents a promising strategy against NSCLC progression.
Keywords:
Apoptosis resistanceNOX4NSCLCNrf2Redox adaptation

More Related Videos

ROS Live Cell Imaging During Neuronal Development09:25

ROS Live Cell Imaging During Neuronal Development

Published on: February 9, 2021

4.9K
Measurements of Physiological Stress Responses in C. Elegans10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

15.1K

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.2K
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
4.3K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
19.3K
Redox Reactions01:27

Redox Reactions

Redox reactions are vital biochemical processes that underpin energy metabolism in cells. These reactions involve the transfer of electrons between molecules, occurring in tandem as oxidation and reduction. Oxidation refers to the loss of electrons, while reduction denotes their gain. This coupling ensures the seamless flow of electrons through metabolic pathways. For example, in bacterial metabolism, glucose undergoes oxidation to carbon dioxide, while oxygen is simultaneously reduced to...
1.3K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
7.2K