2. Academic Validation
  3. Solasonine promotes ferroptosis of hepatoma carcinoma cells via glutathione peroxidase 4-induced destruction of the glutathione redox system

Solasonine promotes ferroptosis of hepatoma carcinoma cells via glutathione peroxidase 4-induced destruction of the glutathione redox system

  • Biomed Pharmacother. 2020 Sep:129:110282. doi: 10.1016/j.biopha.2020.110282.
Mingming Jin 1,  Chunzi Shi 2,  Tian Li 3,  Yue Wu 4,  Cheng Hu 5,  Gang Huang 6
Affiliations

Affiliations

  • 1 Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, PR China; Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, PR China. Electronic address: [email protected].
  • 2 Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, PR China; Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, PR China. Electronic address: [email protected].
  • 3 Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, PR China; Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, PR China. Electronic address: [email protected].
  • 4 Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, PR China; Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, PR China. Electronic address: [email protected].
  • 5 Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, PR China. Electronic address: [email protected].
  • 6 Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, PR China. Electronic address: [email protected].
PMID: 32531676 DOI: 10.1016/j.biopha.2020.110282
Abstract

Solasonine is a compound isolated from Solanum melongena that has Anti-infection properties, and promotes neurogenesis. However, the use of solasonine for the treatment of hepatocellular carcinoma (HCC) has not yet been reported. So, the aim of this study was to assess the efficacy of solasonine for the treatment of HCC. The effects of solasonine were tested using the HCC cell lines HepG2 and HepRG. Metabolomics analysis was conducted to assess the effects of solasonine on tumor growth of nude mice xenografts using HepG2 cells. The data demonstrated that solasonine significantly suppressed proliferation of HepG2 and HepRG cells. A mouse xenograft model of HepG2 tumor formation confirmed that solasonine suppressed tumor volume and weight, and inhibited HCC cell migration and invasion, as determined with the Transwell and scratch wound assays. To further reveal the underlying regulatory mechanism, metabolomics analysis was performed. The results revealed the effects of solasonine on glutathione metabolism, including Glutathione Peroxidase 4 (GPX4) and glutathione synthetase (GSS). The glutathione-dependent lipid hydroperoxidase GPX4 prevents Ferroptosis by converting lipid hydroperoxides into non-toxic lipid alcohols. Ferroptosis has previously been implicated in the cell death that underlies several degenerative conditions, and induction of Ferroptosis by the inhibition of GPX4 has emerged as a therapeutic strategy to trigger Cancer cell death. Solasonine increased lipid ROS levels in HepG2 cells by suppression of GPX4 and GSS. However, the use of a Ferroptosis inhibitor reversed solasonine-induced ROS production and cell Apoptosis. Taken together, these results demonstrate that solasonine promotes Ferroptosis of HCC cells via GPX4-induced destruction of the glutathione redox system.

Keywords

Ferroptosis; Glutathione peroxidase 4; Glutathione redox system; Hepatoma carcinoma; Solasonine.

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