Tremella fuciformis polysaccharides induce ferroptosis in Epstein-Barr virus-associated gastric cancer by inactivating NRF2/HO-1 signaling

Aging (Albany NY). 2024 Jan 19;16(2):1767-1780. doi: 10.18632/aging.205457. Epub 2024 Jan 19.

Abstract

Approximately 10% of gastric cancers are associated with Epstein-Barr virus (EBV). Tremella fuciformis polysaccharides (TFPs) are characterized by antioxidative and anti-inflammatory effects in different diseases. However, whether TFP improves EBV-associated gastric cancer (EBVaGC) has never been explored. The effects of TFP on EBV-infected GC cell viability were determined using a CCK-8 assay and flow cytometry. Western blotting and RT-qPCR were performed to explore the expression of ferroptosis-related proteins. The CCK-8 assay showed that TFP decreased EBV-infected GC cell viability in a dose- and time-dependent manner. Flow cytometry assays indicated that TFP significantly induced EBV-infected GC cell death. TFP also reduced the migratory capacity of EBV-infected GC cells. Furthermore, treatment with TFP significantly increased the mRNA levels of PTGS2 and Chac1 in EBV-infected GC cells. Western blot assays indicated that TFP suppressed the expression of NRF2, HO-1, GPX4 and xCT in EBV-infected GC cells. More importantly, overexpression of NRF2 could obviously rescue TFP-induced downregulation of GPX4 and xCT in EBV-infected GC cells. In summary, we showed novel data that TFP induced ferroptosis in EBV-infected GC cells by inhibiting NRF2/HO-1 signaling. The current findings may shed light on the potential clinical application of TFP in the treatment of EBVaGC.

Keywords: Epstein-Barr virus-associated gastric cancer; NRF2/HO-1; Tremella fuciformis polysaccharides; ferroptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basidiomycota*
  • Epstein-Barr Virus Infections* / complications
  • Ferroptosis*
  • Herpesvirus 4, Human / genetics
  • Humans
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Sincalide / metabolism
  • Stomach Neoplasms* / genetics

Substances

  • NF-E2-Related Factor 2
  • Sincalide

Supplementary concepts

  • Tremella fuciformis