Dataset Information

α-Hederin promotes ferroptosis and reverses cisplatin chemoresistance in non-small cell lung cancer.

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.

SUBMITTER: Han S

PROVIDER: S-EPMC10866401 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

α-Hederin promotes ferroptosis and reverses cisplatin chemoresistance in non-small cell lung cancer.

Han Shugao S Yang Xi X Zhuang Jing J Zhou Qing Q Wang Jingjing J Ru Lixin L Niu Furong F Mao Wei W

Aging 20240118 2

<h4>Background</h4>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 <i>Nigella sativa</i>. The study aims to explore the effects of α-Hederin on cisplatin resistance in NSCLC.<h4>Methods</h4>NSCLC cisplatin-resistant cell lines A549/DPP and PC-9 were cultured to evaluate the efficacy of α-Hederin in the treatment of NSCLC <i>in vitro</i> and <i>i ...[more]

PMID: 38244586

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Dataset Information

α-Hederin promotes ferroptosis and reverses cisplatin chemoresistance in non-small cell lung cancer.

Background

Methods

Results

Conclusion

Publications

α-Hederin promotes ferroptosis and reverses cisplatin chemoresistance in non-small cell lung cancer.

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