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α-Hederin promotes ferroptosis and reverses cisplatin chemoresistance in non-small cell lung cancer.
Han, Shugao; Yang, Xi; Zhuang, Jing; Zhou, Qing; Wang, Jingjing; Ru, Lixin; Niu, Furong; Mao, Wei.
Afiliación
  • Han S; Department of Radiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
  • Yang X; Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou 313000, China.
  • Zhuang J; Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou 313000, China.
  • Zhou Q; Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou 313000, China.
  • Wang J; Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou 313000, China.
  • Ru L; Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou 313000, China.
  • Niu F; School of Medicine, Huzhou Normal University, Huzhou 313000, China.
  • Mao W; Huzhou Hospital of Traditional Chinese Medicine, Zhejiang University of Traditional Chinese Medicine, Huzhou 313000, China.
Aging (Albany NY) ; 16(2): 1298-1317, 2024 01 18.
Article en En | MEDLINE | ID: mdl-38244586
ABSTRACT

BACKGROUND:

Cisplatin is a core chemotherapy regimen in non-small cell lung cancer (NSCLC). However, chemoresistance to cisplatin leads to a poor prognosis in NSCLC. α-Hederin is a natural compound extracted from Nigella sativa. The study aims to explore the effects of α-Hederin on cisplatin resistance in NSCLC.

METHODS:

NSCLC cisplatin-resistant cell lines A549/DPP and PC-9 were cultured to evaluate the efficacy of α-Hederin in the treatment of NSCLC in vitro and in vivo. Metabolomics and RNA-seq analysis were used to determine the potential mechanisms of action of α-Hederin.

RESULTS:

The results showed that α-Hederin inhibited cisplatin-resistant NSCLC cells proliferation and metastasis. Mice xenograft, orthotopic, and metastatic A549/DPP cell models also showed the anti-tumor effects of α-Hederin. The metabolomics and RNA-seq analysis results showed that α-Hederin activated DDIT3/ATF3 pathway and ferroptosis via silencing SLC7A11 and GPX4. Furthermore, α-Hederin enhanced the nuclear expression of EGR1. Bioinformatics and luciferase experiments confirmed that EGR1 binds to the miR-96-5p promoter region, inhibiting transcription. In addition, miR-96-5p directly suppressed the levels of DDIT3.

CONCLUSION:

This study revealed that α-Hederin activated EGR1 nuclear translocation and directly repressed miR-96-5p. It also promoted DDIT3/ATF3-mediated ferroptosis and reversed cisplatin resistance in NSCLC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Saponinas / Carcinoma de Pulmón de Células no Pequeñas / MicroARNs / Ferroptosis / Neoplasias Pulmonares Límite: Animals / Humans Idioma: En Revista: Aging (Albany NY) Asunto de la revista: GERIATRIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Saponinas / Carcinoma de Pulmón de Células no Pequeñas / MicroARNs / Ferroptosis / Neoplasias Pulmonares Límite: Animals / Humans Idioma: En Revista: Aging (Albany NY) Asunto de la revista: GERIATRIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos