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Reuterin promotes pyroptosis in hepatocellular cancer cells through mtDNA-mediated STING activation and caspase 8

Lin Cui1, Xiaohui Xu1, Hui Fan1

  • 1Department of Biochemistry and Molecular Biology, and Molecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China.

Cancer Letters
|August 17, 2024
PubMed

Insights

Reuterin, a metabolite from Lactobacillus reuteri, shows potential against hepatocellular carcinoma (HCC) by inducing cell death. It may enhance sorafenib treatment for liver cancer.

Area of Science:

  • Oncology
  • Microbiology
  • Immunology

Background:

  • Hepatocellular carcinoma (HCC) presents a significant clinical challenge due to limited treatment options and poor prognosis.
  • There is a critical need for novel therapeutic strategies, including new drugs and combination therapies, to combat advanced HCC.

Purpose of the Study:

  • To investigate the anti-HCC potential of reuterin, a metabolite of Lactobacillus reuteri.
  • To elucidate the molecular mechanisms underlying reuterin's anti-tumor effects and its synergy with sorafenib.

Main Methods:

  • Assessing reuterin's impact on HCC cell viability and death pathways.
  • Analyzing the effects of reuterin on mitophagy, mitochondrial DNA (mtDNA) replication, mitochondrial fission, and STING activation.
  • Investigating the roles of caspase 8 and RIPK3 in reuterin-induced cell death.

Main Results:

  • Reuterin demonstrated significant anti-HCC potential, impairing mitophagy and mtDNA replication.
  • Reuterin induced STING activation, leading to pyroptosis and necroptosis, with pyroptosis being the predominant cell death pathway.
  • Reuterin treatment upregulated caspase 8, which cleaved RIPK3, thereby inhibiting necroptosis and promoting pyroptosis.

Conclusions:

  • Reuterin exhibits potent anti-cancer properties against HCC by disrupting mitochondrial function and activating STING-mediated cell death.
  • Reuterin's mechanism involves promoting pyroptosis as the primary mode of cancer cell death.
  • Reuterin holds promise as a combinational therapeutic agent for HCC, potentially enhancing existing treatments like sorafenib.
Keywords:
Hepatocellular carcinomaPyroptosisReuterinSTINGmtDNA

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