Related Experiment Video

Updated: May 23, 2025

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
00:06

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

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Simultaneous activation and blockade of autophagy to fight hepatocellular carcinoma

Hala Shalhoub1,2, Patrick Gonzalez1,2, Alexandre Dos Santos1,2

  • 1INSERM, U1193, Paul-Brousse University Hospital, Hepatobiliary Centre, Villejuif, France.

Autophagy Reports
|May 21, 2025
PubMed

Insights

Autophagy manipulation is a promising strategy for hepatocellular carcinoma (HCC) treatment. Combining sodium butyrate (NaB) and chloroquine (CQ) synergistically kills liver cancer cells by inducing autophagosome accumulation and oxidative stress.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Hepatocellular carcinoma (HCC) remains difficult to treat due to its heterogeneity.
  • Pharmacological targeting of autophagy is being explored for HCC treatment and chemosensitization.
  • Autophagy marker proteins (p62 and LC3) show significant variability in HCC tissues, indicating heterogeneous autophagic flux.

Purpose of the Study:

  • To investigate a non-personalized autophagy targeting strategy for HCC.
  • To evaluate the combined effect of autophagy activation and blockade on HCC cell lines.
  • To explore the underlying mechanisms of cancer cell death induced by this combination therapy.

Main Methods:

  • Analysis of p62 and LC3 protein levels in paired HCC tumor and non-tumor tissues.
  • In vitro treatment of human liver cancer cell lines with sodium butyrate (NaB) and chloroquine (CQ).
  • Assessment of cancer cell death, autophagosome accumulation, lysosome membrane permeabilization (LMP), and oxidative stress.

Main Results:

  • Significant variability in p62 and LC3-II levels observed between HCC tumors and adjacent non-tumor tissues.
  • The combination of NaB (autophagy inducer) and CQ (autophagy blocker) demonstrated marked synergistic cytotoxic effects on HCC cell lines.
  • No deleterious effects were observed on normal hepatocytes in culture.
  • Cancer cell death was associated with increased autophagosomes, LMP, and oxidative stress.

Conclusions:

  • Simultaneous activation and blockade of autophagy represent a potential valuable therapeutic approach against HCC.
  • This combined strategy may benefit a broad range of HCC patients, irrespective of their tumor's specific autophagic flux.
  • Microbiota-derived products may enhance the sensitivity of HCC cells to antitumor agents.
Keywords:
Liver cancerbutyratecell deathchloroquinecholangiocarcinomamicrobial metaboliteoxidative stresstherapy

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