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Pseudolaric acid B promotes lung cancer cells ferroptosis depending on JNK/ERK-mediated upregulation of survivin
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  • Published: 11 February 2026

Pseudolaric acid B promotes lung cancer cells ferroptosis depending on JNK/ERK-mediated upregulation of survivin

  • Yuqiong Li1,2 na1,
  • Changping Yu2 na1,
  • Shufeng Yang2,
  • Buqing Sai3,
  • Xin Chen1,
  • Ping Chen2,
  • Huoyan Liu2,
  • Jie Jia2,
  • Yu Zhang2,
  • Ruifen Sun1 &
  • …
  • Shaoqing Shi2 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Cancer
  • Cell biology

Abstract

Lung cancer is one of the most common malignant tumors worldwide, seriously threatening human health. PAB (pseudolaric acid B), an extract of pseudolarix amabilis, has exhibited notable anticancer properties. Nevertheless, the molecular mechanisms underlying PAB-induced anticancer activities remain controversial in lung cancer especially. Herein we aim to investigate the role of IAPs in PAB-induced anticancer effects. PAB selectively inhibits the viability of lung cancer cells and downregulates the expression of IAPs. Transcriptomic analysis suggests that PAB induces lung cancer cells ferroptosis. PAB indeed promotes ferroptotic cell death since PAB enhances lipid oxidation and Fe2+ content. Interestingly, PAB markedly enhances Survivin expression. Suppression of Survivin abolishes PAB-induced ferroptosis. PAB significantly strengthens JNK and ERK kinase activities. We further demonstrate suppression of JNK/ERK reversed PAB-mediated-cytotoxicity, meanwhile restores the expression of Survivin and ferroptosis-related proteins. Consistently, xenograft tumor model results also support that PAB induces ferroptosis through Survivin upregulation. Collectively, we demonstrate PAB induces ferroptosis in lung cancer cells in vivo and in vitro depending on JNK and ERK-mediated Survivin upregulation, providing novel insight for clinical administration of PAB in lung cancer.

Data availability

Genes related to ferroptosis are available on the FerrDb portal (http://www.zhounan.org/ferrdb/current/).The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive (Genomics, Proteomics & Bioinformatics 2017) in BIG Data Center (Nucleic Acids Res 2017), Beijing Institute of Genomics (BIG), Chinese Academy of Sciences, under accession numbers HRA013555 that are publicly accessible at https://ngdc.cncb.ac.cn/gsa-human/.The data generated in the present study may be requested from the corresponding author.

Abbreviations

AMPK:

adenosine 5’-monophosphate (AMP)-activated protein kinase

Bax:

Bcl2-associated X protein

Bcl2:

B-cell lymphoma 2

CQ:

chloroquine

CDK1:

cyclin-dependent kinases

c-IAP1:

cellular inhibitor of apoptosis 1

c-IAP2:

cellular inhibitor of apoptosis 2

DFO:

deferoxamine

ERK:

extracellular regulated protein kinases

GPX4:

glutathione peroxidase 4

HSP60:

heat shock protein 60

IAPs:

inhibitor of apoptosis proteins

IHC:

immunohistochemistry

JNK:

c-Jun N-terminal kinase

KEGG:

Kyoto Encyclopedia of Genes and Genomes

MMP:

mitochondrial membrane potential

MAPKs:

mitogen-activated protein kinase

NAIP:

NLR family apoptosis inhibitory protein

NCOA4:

nuclear Receptor Coactivator 4

NSCLC:

non-small cell lung cancer

PAB:

pseudolaric acid B

PARP:

poly ADP-ribose polymerase

RCD:

non-apoptotic regulated cell death

ROS:

reactive oxygen species

SLC7A11:

solute carrier family 7 member 11

TCM:

traditional Chinese Medicine

XIAP:

X-linked inhibitor of apoptosis protein

4-HNE:

4-Hydroxynonenal

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Acknowledgements

We are grateful for the technical support provided by the instrument sharing platform of Kunming Medical University and Yunnan University of Traditional Chinese Medicine.We thank Dr.Yasir Hameed and Dr.Mirza Imran Shahzad for their assistance with experimental work and data curation.

Funding

This work are supported by Yunnan Applied Basic Research Program (202201AT070043); National Natural Science Foundation of China (82460562, 82160581, 81560429); Yunnan Health training project of high level talents (D-2024001), 535 High Talent Project of First Affiliated Hospital of Kunming Medical University (2022535Q02); Yunnan Revitalization Talent Support Program, Yunnan Science Foundation of China (2019FF002(-011)); Yunnan Key Laboratory of Organ Transplantation (202449CE340016); The National Administration of Traditional Chinese Medicine High-level Key Discipline Construction Project “Dai Medicine”.

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  1. Yuqiong Li and Changping Yu contributed equally to this work.

Authors and Affiliations

  1. Department of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, No. 1076th, Yuhua Road, Chenggong, Kunming, 650500, Yunnan, China

    Yuqiong Li, Xin Chen & Ruifen Sun

  2. Department of Clinical Research Center, First Affiliated Hospital of Kunming Medical University, No. 295th, Xichang Road, Wuhua, Kunming, 650000, Yunnan, China

    Yuqiong Li, Changping Yu, Shufeng Yang, Ping Chen, Huoyan Liu, Jie Jia, Yu Zhang & Shaoqing Shi

  3. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Kunming Medical University, Kunming, 650500, Yunnan, China

    Buqing Sai

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Yuqiong Li and Changping Yu wrote the original manuscript text and Ruifen Sun and Shaoqing Shi review and editing the original manuscript text and Buqing Sai provide financial support. All authors reviewed the manuscript.

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All animal experiments were conducted in accordance with the ARRIVE guidelines and were approved by the Animal Experiment Ethics Committee of Kunming Medical University Laboratory Animal (approval number: kmmu20230490). Euthanasia was performed by intraperitoneal injection of pentobarbital sodium (150 mg/kg)29,30. All procedures were carried out by trained personnel to ensure animal welfare and minimize suffering.

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Li, Y., Yu, C., Yang, S. et al. Pseudolaric acid B promotes lung cancer cells ferroptosis depending on JNK/ERK-mediated upregulation of survivin. Sci Rep (2026). https://doi.org/10.1038/s41598-026-36423-3

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  • Received: 25 June 2025

  • Accepted: 13 January 2026

  • Published: 11 February 2026

  • DOI: https://doi.org/10.1038/s41598-026-36423-3

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Keywords

  • Lung cancer
  • PAB
  • Ferroptosis
  • Survivin
  • MAPKs
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