Related Experiment Video

Updated: Feb 28, 2026

Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy
07:40

Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy

Published on: May 26, 2023

1.7K

Isodeoxyelephantopin induces protective autophagy in lung cancer cells via Nrf2-p62-keap1 feedback loop

Yang Wang1, Jing Zhang1, Zhi-Hao Huang1

  • 1Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China.

Cell Death & Disease
|June 16, 2017
PubMed

Insights

Isodeoxyelephantopin (ESI) activates protective autophagy via a Nrf2-p62-Keap1 feedback loop in lung cancer cells. Targeting this pathway enhances ESI

Area of Science:

  • * Oncology
  • * Molecular Biology
  • * Pharmacology

Background:

  • * Isodeoxyelephantopin (ESI), derived from Elephantopus scaber L., exhibits anticancer properties.
  • * Cancer cells may develop protective mechanisms against ESI treatment.
  • * Understanding these responses is crucial for optimizing ESI's therapeutic potential.

Purpose of the Study:

  • * To investigate the protective responses of cancer cells to ESI treatment.
  • * To elucidate the molecular mechanisms underlying ESI's effects on autophagy and oxidative stress.
  • * To explore the potential of targeting the Nrf2-p62-Keap1 axis in combination with ESI therapy.

Main Methods:

  • * Confocal fluorescence microscopy to assess autophagy flux using mCherry-EGFP-LC3 reporter.
  • * Western blotting to quantify autophagy markers (LC3-II, ATG3, Beclin1).
  • * SILAC quantitative proteomics and bioinformatics analysis to identify ESI-regulated proteins and pathways.
  • * Gene knockdown (Nrf2, p62) to validate the role of the Nrf2-p62-Keap1 axis.

Main Results:

  • * ESI significantly induced autophagy flux and increased autophagy marker expression in lung cancer cells.
  • * ESI treatment led to Nrf2 nuclear translocation and activation of downstream targets HO-1 and p62.
  • * ESI-induced p62 formed a positive feedback loop with Keap1, promoting Nrf2 activation and autophagy.
  • * Autophagy inhibition (3-MA) enhanced ESI's cytotoxicity, while Nrf2 or p62 knockdown abrogated ESI-induced autophagy and increased ESI's anticancer effects.

Conclusions:

  • * ESI activates a protective Nrf2-p62-Keap1 feedback loop that promotes autophagy, aiding cancer cell survival.
  • * Inhibiting this regulatory axis in combination with ESI treatment presents a promising anticancer strategy.

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...
10.1K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.8K
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.6K