Evidence map›Paper›PMID 37056925›Full record

ArticleInternational journal of biological sciences2023

Timosaponin AIII promotes non-small-cell lung cancer ferroptosis through targeting and facilitating HSP90 mediated GPX4 ubiquitination and degradation.

Cong Zhou, Ting Yu, Rui Zhu, Junjie Lu, Xiaohu Ouyang, Zili Zhang, Qianyun Chen, Junyi Li, Jing Cui, Feng Jiang and 6 more

Open access · goldAbstract read
In one paragraph

Article in International journal of biological sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 1 pooled it
38.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

92 citing papers in PubMed, 1 synthesis or guideline pooled it, 149 citations in OpenAlex.

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32 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 3 countries.

Cong ZhouDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ting YuDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Rui ZhuDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Junjie LuDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xiaohu OuyangDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Zili ZhangDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Qianyun ChenDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Junyi LiDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Jing CuiHealth Management Center, Hubei Provincial Hospital of Integrated Chinese & Western Medicine, Wuhan, China.
Feng JiangCollege of International Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Kim Yun JinSchool of Traditional Chinese Medicine, Xiamen University Malaysia, Selangor. 43900. Malaysia.
Alexey SarapultsevRussian-Chinese Education and Research Center of System Pathology, South Ural State University, 454080 Chelyabinsk, Russia.
Fangfei LiShum Yiu Foon Sum Bik Chuen Memorial Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, 999077, Hong Kong SAR, China.
Ge ZhangInstitute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
Shanshan LuoInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Desheng HuDepartment of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Union Hospital · CNHuazhong University of Science and Technology · CNHong Kong Baptist University · HKInstitute of Immunology and Physiology · RUTianjin University of Traditional Chinese Medicine · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Timosaponin AIII (Tim-AIII), a steroid saponin, exhibits strong anticancer activity in a variety of cancers, especially breast cancer and liver cancer. However, the underlying mechanism of the effects of Tim-AIII-mediated anti-lung cancer effects remain obscure. In this study, we showed that Tim-AIII suppressed cell proliferation and migration, induced G2/M phase arrest and ultimately triggered cell death of non-small cell lung cancer (NSCLC) cell lines accompanied by the release of reactive oxygen species (ROS) and iron accumulation, malondialdehyde (MDA) production, and glutathione (GSH) depletion. Interestingly, we found that Tim-AIII-mediated cell death was reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Meanwhile, the heat shock protein 90 (HSP90) was predicted and verified as the direct binding target of Tim-AIII by SwissTargetPrediction (STP) and surface plasmon resonance (SPR) assay. Further study showed that Tim-AIII promoted HSP90 expression and Tim-AIII induced cell death was blocked by the HSP90 inhibitor tanespimycin, indicating that HSP90 was the main target of Tim-AIII to further trigger intracellular events. Mechanical analysis revealed that the Tim-AIII-HSP90 complex further targeted and degraded glutathione peroxidase 4 (GPX4), and promoted the ubiquitination of GPX4, as shown by an immunoprecipitation, degradation and

Indexed as

Carcinoma, Non-Small-Cell LungFerroptosisLung NeoplasmsSaponinsAnimalsHSP90 Heat-Shock ProteinsHumansIronMiceMice, Inbred C57BLMice, NudePeroxidasesReactive Oxygen SpeciesSteroidsUbiquitinationHSP90 Heat-Shock ProteinsIronPeroxidasesphospholipid hydroperoxide cysteine peroxidaseReactive Oxygen SpeciesSaponinsSteroidstimosaponin AIIIferroptosisglutathione peroxidase 4heat shock protein 90non-small cell lung cancerTimosaponin AIII

Identifiers

PMID37056925
PMCPMC10086754
OpenAlexW4324010199

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.