2. Academic Validation
  3. Regulatory mechanism of α-hederin upon cisplatin sensibility in NSCLC at safe dose by destroying GSS/GSH/GPX2 axis-mediated glutathione oxidation-reduction system

Regulatory mechanism of α-hederin upon cisplatin sensibility in NSCLC at safe dose by destroying GSS/GSH/GPX2 axis-mediated glutathione oxidation-reduction system

  • Biomed Pharmacother. 2022 Jun;150:112927. doi: 10.1016/j.biopha.2022.112927.
Yue Wu 1,  Dongliang Wang 2,  Yuqing Lou 3,  Xiyu Liu 4,  Pinzheng Huang 5,  Mingming Jin 6,  Gang Huang 7
Affiliations

Affiliations

  • 1 Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China. Electronic address: wy18236989057@126.com.
  • 2 Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China. Electronic address: wdl0106@163.com.
  • 3 Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China. Electronic address: 2019_lyq@shutcm.edu.cn.
  • 4 Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China. Electronic address: Liuxiyu199509@163.com.
  • 5 School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China. Electronic address: 193832401@st.usst.edu.cn.
  • 6 Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China. Electronic address: asdjinmingming@126.com.
  • 7 Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China. Electronic address: huanggang@sumhs.edu.cn.
PMID: 35398749 DOI: 10.1016/j.biopha.2022.112927
Abstract

Emerging studies showed that α-hederin induced autophagic cell death in different cancers via Reactive Oxygen Species. Nevertheless, α-hederin role in non-small-cell lung Cancer (NSCLC) remains unknown. So, the aim of this study was to explain whether Ferroptosis is a therapeutic strategy to NSCLC, and to explore the effect of α-hederin on NSCLC Ferroptosis. Current investigation found that α-hederin inhibited NSCLC cell proliferation, invasion, and migration in vitro and in vivo at toxic doses. The α-hederin treatment also increased NSCLC cell chemosensitivity to cisplatin and promoted Ferroptosis and Apoptosis at a safe dose. Proteomics, metabolomics, and high-throughput sequencing detection confirmed that α-hederin treatment downregulated Glutathione Peroxidase 2 (GPX2), and glutathione synthase (GSS) expression suppressed the synthesis of glutathione (GSH), which destroyed the GSH redox system. Eventually, it led to Ferroptosis, Apoptosis, and membrane permeabilization in NSCLC. Taken together, the study provided molecular data to confirm that α-hederin induced Ferroptosis, Apoptosis, and membrane permeabilization in NSCLC by destroying the GSS/GSH/GPX2 axis-mediated GSH oxidation-reduction system at a safe and low-toxicity dose.

Keywords

Apoptosis; Ferroptosis; Glutathione oxidation-reduction system; NSCLC; α-hederin.

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