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Updated: Jul 15, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

Ciclopirox suppresses melanoma growth by activating ER stress-driven apoptosis and disrupting Src/STAT3 signaling

Ziwei Zhang1, Junwan Lu2, Zheng Ouyang1

  • 1National Health Commission Key Laboratory of Birth Defect Research and Prevention & MOE Key Lab of Rare Pediatric Diseases, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang 421001, China.

Acta Biochimica Et Biophysica Sinica
|July 13, 2026
PubMed

Insights

Ciclopirox (CPX), an antifungal drug, effectively inhibits melanoma cell growth and tumor development. It works by inducing oxidative stress and endoplasmic reticulum stress, leading to apoptosis, and by disrupting the Src/STAT3 signaling pathway.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Ciclopirox (CPX) is an FDA-approved antifungal agent.
  • CPX demonstrates potential antitumor properties, particularly against melanoma.

Purpose of the Study:

  • To investigate the efficacy of CPX against melanoma.
  • To elucidate the underlying mechanisms of CPX's antitumor activity.

Main Methods:

  • In vitro assays for cell proliferation, migration, and invasion.
  • In vivo xenograft tumor growth suppression studies.
  • Analysis of mitochondrial dysfunction, reactive oxygen species (ROS) generation, and endoplasmic reticulum (ER) stress.
  • Investigation of apoptosis markers (Caspase-3 activation).
  • Assessment of CPX's effect on Src and STAT3 signaling pathways.

Main Results:

  • CPX potently inhibited melanoma cell proliferation, migration, and invasion in vitro.
  • CPX significantly suppressed xenograft tumor growth in vivo.
  • CPX induced mitochondrial dysfunction, ROS production, and PERK-dependent ER stress, leading to apoptosis.
  • Antioxidant treatment rescued CPX-induced apoptosis, confirming the role of oxidative stress.
  • CPX directly inhibited Src kinase activity and disrupted STAT3 phosphorylation and expression.
  • CPX demonstrated a multi-level disruption of the Src/STAT3 signaling pathway.

Conclusions:

  • CPX exhibits significant anti-melanoma effects through dual mechanisms.
  • These mechanisms involve ROS/ER stress-mediated apoptosis and disruption of the Src/STAT3 pathway.
  • CPX represents a potential therapeutic repurposing candidate for melanoma treatment.
Keywords:
Src/STAT3 signalingapoptosisciclopirox (CPX)drug repurposingendoplasmic reticulum stressmelanoma

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