Evidence map›Paper›PMID 26758418›Full record

ArticleOncotarget2016

EM23, a natural sesquiterpene lactone, targets thioredoxin reductase to activate JNK and cell death pathways in human cervical cancer cells.

Fang-Yuan Shao, Sheng Wang, Hong-Yu Li, Wen-Bo Chen, Guo-Cai Wang, Dong-Lei Ma, Nai Sum Wong, Hao Xiao, Qiu-Ying Liu, Guang-Xiong Zhou and 4 more

Abstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

  1. Ethyl acetate extract ofResearch in pharmaceutical sciences · 2026
    Article
  2. Article
  3. Natural and Synthetic Lactones Possessing Antitumor Activities.International journal of molecular sciences · 2021
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
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

14 authors.

Fang-Yuan ShaoGuangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, China.
Sheng WangGuangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, China.
Hong-Yu LiCollege of Pharmacy, Jinan University, Guangzhou, China.
Wen-Bo ChenGuangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, China.
Guo-Cai WangCollege of Pharmacy, Jinan University, Guangzhou, China.
Dong-Lei MaGuangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, China.
Nai Sum WongDepartment of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
Hao XiaoUniversity of The Chinese Academy of Sciences, Beijing, China.
Qiu-Ying LiuGuangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, China.
Guang-Xiong ZhouCollege of Pharmacy, Jinan University, Guangzhou, China.
Yao-Lan LiCollege of Pharmacy, Jinan University, Guangzhou, China.
Man-Mei LiCollege of Pharmacy, Jinan University, Guangzhou, China.
Yi-Fei WangGuangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, China.
Zhong LiuGuangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sesquiterpene lactones (SLs) are the active constituents of a variety of medicinal plants and found to have potential anticancer activities. However, the intracellular molecular targets of SLs and the underlying molecular mechanisms have not been well elucidated. In this study, we observed that EM23, a natural SL, exhibited anti-cancer activity in human cervical cancer cell lines by inducing apoptosis as indicated by caspase 3 activation, XIAP downregulation and mitochondrial dysfunction. Mechanistic studies indicated that EM23-induced apoptosis was mediated by reactive oxygen species (ROS) and the knockdown of thioredoxin (Trx) or thioredoxin reductase (TrxR) resulted in a reduction in apoptosis. EM23 attenuated TrxR activity by alkylation of C-terminal redox-active site Sec498 of TrxR and inhibited the expression levels of Trx/TrxR to facilitate ROS accumulation. Furthermore, inhibition of Trx/TrxR system resulted in the dissociation of ASK1 from Trx and the downstream activation of JNK. Pretreatment with ASK1/JNK inhibitors partially rescued cells from EM23-induced apoptosis. Additionally, EM23 inhibited Akt/mTOR pathway and induced autophagy, which was observed to be proapoptotic and mediated by ROS. Together, these results reveal a potential molecular mechanism for the apoptotic induction observed with SL compound EM23, and emphasize its putative role as a therapeutic agent for human cervical cancer.

Indexed as

ApoptosisCell DeathCell Line, TumorEnzyme ActivationFemaleHL-60 CellsHumansK562 CellsLactonesMAP Kinase Kinase 4MCF-7 CellsReactive Oxygen SpeciesSesquiterpenesThioredoxin-Disulfide ReductaseTransfectionUterine Cervical NeoplasmsEM23 sesquiterpeneLactonesMAP Kinase Kinase 4Reactive Oxygen SpeciesSesquiterpenesThioredoxin-Disulfide ReductaseapoptosisROSsesquiterpene lactonethioredoxinthioredoxin reductase

Identifiers

PMID26758418
PMCPMC4872749

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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.