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

• Published in: Aging (Albany, NY.) Vol. 16; no. 2; pp. 1767 - 1780
• Main Authors: Kong, Wencheng, Liu, Xinchun, Zhu, Hangzhang, Zheng, Sixing, Yin, Guang, Yu, Panpan, Shan, Yuqiang, Ma, Shenglin, Ying, Rongchao, Jin, Huicheng
• Format: Journal Article
• Language: English
• Published: United States Impact Journals 19.01.2024
• Subjects: Basidiomycota; Epstein-Barr Virus Infections - complications; Ferroptosis; Herpesvirus 4, Human - genetics; Humans; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Research Paper; Sincalide - metabolism; Stomach Neoplasms - genetics; NRF2/HO-1; ferroptosis; Tremella fuciformis polysaccharides; Epstein-Barr virus-associated gastric cancer
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.205457

Approximately 10% of gastric cancers are associated with Epstein-Barr virus (EBV). 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.