Related Experiment Video

Updated: Apr 16, 2026

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
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Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity

Published on: October 17, 2025

652

Autophagy protects against dasatinib-induced hepatotoxicity via p38 signaling

Xiaochun Yang1, Jincheng Wang1, Jiabin Dai1

  • 1Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

Oncotarget
|March 10, 2015
PubMed

Insights

Dasatinib treatment can cause liver damage, but autophagy acts as a protective mechanism. Activating p38 signaling enhances this protective autophagy, mitigating dasatinib-induced liver injury without impacting its anti-cancer effects.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Pharmacology

Background:

  • Dasatinib, a tyrosine kinase inhibitor, can cause liver dysfunction, with the underlying mechanisms poorly understood.
  • Autophagy plays a dual role in liver injury, acting as either a survival or death pathway.
  • Oxidative stress is implicated in both autophagy and drug-induced hepatotoxicity.

Purpose of the Study:

  • To investigate the role of autophagy in dasatinib-induced liver injury.
  • To elucidate the signaling pathways involved in dasatinib-induced hepatotoxicity.
  • To explore therapeutic strategies for preventing dasatinib-associated liver damage.

Main Methods:

  • Induction of autophagy in response to dasatinib treatment.
  • Assessment of liver damage markers and autophagy markers (LC3-II, p62).
  • Investigation of the p38 signaling pathway and its role in autophagy and hepatotoxicity.
  • Evaluation of a p38 agonist (isoproterenol hydrochloride) in mitigating liver injury.

Main Results:

  • Autophagy is induced during dasatinib-induced liver damage, suggesting a protective role.
  • Inhibition of autophagy worsened dasatinib-induced liver failure.
  • Dasatinib activates the p38 signaling pathway, which mediates the protective effects of autophagy.
  • p38 activation alleviated liver injury by enhancing autophagy, without compromising dasatinib's anti-cancer efficacy.

Conclusions:

  • Autophagy acts as a survival mechanism against dasatinib-induced hepatotoxicity.
  • The p38 signaling pathway is crucial for activating protective autophagy in liver injury.
  • Targeting p38-mediated autophagy presents a potential therapeutic strategy to manage dasatinib-induced liver damage.
Keywords:
autophagydasatinibhepatotoxicityp38 signaling

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