2. Academic Validation
  3. Epigallocatechin gallate modulates ferroptosis through downregulation of tsRNA-13502 in non-small cell lung cancer

Epigallocatechin gallate modulates ferroptosis through downregulation of tsRNA-13502 in non-small cell lung cancer

  • Cancer Cell Int. 2024 Jun 5;24(1):200. doi: 10.1186/s12935-024-03391-5.
Shun Wang # 1,  Ruohuang Wang # 2,  Dingtao Hu 3,  Caoxu Zhang 4,  Peng Cao 5,  Jie Huang 6,  Baoqing Wang 7 8
Affiliations

Affiliations

  • 1 Department of Respiratory Medicine, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China.
  • 2 Department of Otolaryngology, The Second Affiliated Hospital of the Naval Military Medical University (Shanghai Changzheng Hospital), Shanghai, 200003, China.
  • 3 Clinical Cancer Institute, Center for Translational Medicine, Naval Medical University, Shanghai, 200433, China.
  • 4 State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics, Department of Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China.
  • 5 Department of Interventional Pulmonology，Anhui Chest Hospital, Hefei, 230022, China.
  • 6 Department of Respiratory Medicine, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China. syarhuang@163.com.
  • 7 Department of Respiratory Medicine, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China. Wang.baoqing@zs-hospital.sh.cn.
  • 8 Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200031, China. Wang.baoqing@zs-hospital.sh.cn.
  • # Contributed equally.
PMID: 38840243 DOI: 10.1186/s12935-024-03391-5
Abstract

Ferroptosis, an iron-dependent regulated cell death mechanism, holds significant promise as a therapeutic strategy in oncology. In the current study, we explored the regulatory effects of epigallocatechin gallate (EGCG), a prominent polyphenol in green tea, on Ferroptosis and its potential therapeutic implications for non-small cell lung Cancer (NSCLC). Treatment of NSCLC cell lines with varying concentrations of EGCG resulted in a notable suppression of cell proliferation, as evidenced by a reduction in Ki67 immunofluorescence staining. Western blot analyses demonstrated that EGCG treatment led to a decrease in the expression of Glutathione Peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) while increasing the levels of acyl-CoA synthetase long-chain family member 4 (ACSL4). These molecular changes were accompanied by an increase in intracellular iron, malondialdehyde (MDA), and Reactive Oxygen Species (ROS), alongside ultrastructural alterations characteristic of Ferroptosis. Through small RNA Sequencing and RT-qPCR, transfer RNA-derived small RNA 13502 (tsRNA-13502) was identified as a significant target of EGCG action, with its expression being upregulated in NSCLC tissues compared to adjacent non-tumorous tissues. EGCG was found to modulate the Ferroptosis pathway by downregulating tsRNA-13502 and altering the expression of key Ferroptosis regulators (GPX4/SLC7A11 and ACSL4), thereby promoting the accumulation of iron, MDA, and ROS, and ultimately inducing Ferroptosis in NSCLC cells. This study elucidates EGCG's multifaceted mechanisms of action, underscoring the modulation of Ferroptosis as a viable therapeutic approach for enhancing NSCLC treatment outcomes.

Keywords

Epigallocatechin gallate (EGCG); Ferroptosis; NSCLC; tsRNA.

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