Related Experiment Video

Updated: Dec 24, 2025

Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
11:02

Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development

Published on: October 30, 2013

21.6K

Miconazole Contributes to NRF2 Activation by Noncanonical P62-KEAP1 Pathway in Bladder Cancer Cells

Te-Fu Tsai1,2, Po-Chun Chen3,4, Yi-Chia Lin1,2

  • 1Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.

Drug Design, Development and Therapy
|April 11, 2020
PubMed
Abstract

Insights

Miconazole significantly activates Nuclear factor (erythroid-derived 2)-like 2 (NRF2) in bladder cancer cells. This activation, mediated by the p62-KEAP1 pathway and reactive oxygen species, suggests potential cancer chemopreventive effects.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a transcription factor crucial for chemoprevention, inflammation, and aging.
  • NRF2 is recognized as a potential target for cancer chemoprevention strategies.
  • Miconazole, a fungicide, exhibits promising antiproliferative effects against cancer cells.

Purpose of the Study:

  • To investigate the mechanism by which miconazole stimulates NRF2 activation in bladder cancer cells.
  • To explore the role of the p62-KEAP1 pathway and reactive oxygen species (ROS) in miconazole-induced NRF2 activation.

Main Methods:

  • Analysis of p62-KEAP1-NRF2 pathway activation using qPCR and Western blot.
  • Confirmation of NRF2 nuclear translocation via immunofluorescence.
  • Detection of ROS production using CM-H2DCFDA staining.

Main Results:

  • Miconazole treatment dose- and time-dependently increased NRF2 activation in bladder cancer cells.
  • p62 expression increased, while the negative regulator KEAP1 expression decreased, following miconazole exposure.
  • Miconazole-induced ROS production was essential for NRF2 activation and nuclear translocation, as demonstrated by ROS scavenger experiments.

Conclusions:

  • Miconazole activates the noncanonical p62-KEAP1-NRF2 pathway in bladder cancer cells.
  • ROS production plays a critical role in mediating miconazole-induced NRF2 activation.
  • The findings elucidate the mechanism of miconazole's NRF2 stimulation, suggesting its potential in cancer chemoprevention.
Keywords:
KEAP1NRF2bladder cancermiconazolep62

More Related Videos

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma13:18

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma

Published on: March 3, 2023

1.6K

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...
9.7K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K