Evidence map›Paper›PMID 28816233›Full record

ArticleActa pharmacologica Sinica2017

Shikonin induces glioma cell necroptosis in vitro by ROS overproduction and promoting RIP1/RIP3 necrosome formation.

Bin Lu, Xu Gong, Zong-Qi Wang, Ye Ding, Chen Wang, Tian-Fei Luo, Mei-Hua Piao, Fan-Kai Meng, Guang-Fan Chi, Yi-Nan Luo and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Acta pharmacologica Sinica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
3.5field-weighted citation impact, top 6% 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

79 citing papers in PubMed, 154 citations in OpenAlex.

  1. Review
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  4. Research status of several programmed cell death in the toxic effect of AFBApoptosis : an international journal on programmed cell death · 2026
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19 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

11 authors at 3 institutions in 1 country.

Bin LuDepartment of Neurosurgery, First Hospital of Jilin University, Changchun 130021, China.
Xu GongDepartment of Hand Surgery, First Hospital of Jilin University, Changchun 130021, China.
Zong-Qi WangDepartment of Neurosurgery, First Hospital of Jilin University, Changchun 130021, China.
Ye DingDepartment of Neurosurgery, First Hospital of Jilin University, Changchun 130021, China.
Chen WangDepartment of Neurosurgery, First Hospital of Jilin University, Changchun 130021, China.
Tian-Fei LuoResearch Center of Neuroscience, First Hospital of Jilin University, Changchun 130021, China.
Mei-Hua PiaoDepartment of Anesthesiology, First Hospital of Jilin University, Changchun 130021, China.
Fan-Kai MengDepartment of Neurosurgery, People's Hospital of Jilin Province, Changchun 130021, China.
Guang-Fan ChiKey Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China.
Yi-Nan LuoDepartment of Neurosurgery, First Hospital of Jilin University, Changchun 130021, China.
Peng-Fei GeDepartment of Neurosurgery, First Hospital of Jilin University, Changchun 130021, China.
Jilin University · CNFirst Hospital of Jilin University · CNPeople 's Hospital of Jilin Province · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Necroptosis is a type of programmed necrosis regulated by receptor interacting protein kinase 1 (RIP1) and RIP3. Necroptosis is found to be accompanied by an overproduction of reactive oxygen species (ROS), but the role of ROS in regulation of necroptosis remains elusive. In this study, we investigated how shikonin, a necroptosis inducer for cancer cells, regulated the signaling leading to necroptosis in glinoma cells in vitro. Treatment with shikonin (2-10 μmol/L) dose-dependently triggered necrosis and induced overproduction of intracellular ROS in rat C6 and human SHG-44, U87 and U251 glioma cell lines. Moreover, shikonin treatment dose-dependently upregulated the levels of RIP1 and RIP3 and reinforced their interaction in the glioma cells. Pretreatment with the specific RIP1 inhibitor Nec-1 (100 μmol/L) or the specific RIP3 inhibitor GSK-872 (5 μmol/L) not only prevented shikonin-induced glioma cell necrosis but also significantly mitigated the levels of intracellular ROS and mitochondrial superoxide. Mitigation of ROS with MnTBAP (40 μmol/L), which was a cleaner of mitochondrial superoxide, attenuated shikonin-induced glioma cell necrosis, whereas increasing ROS levels with rotenone, which improved the mitochondrial generation of superoxide, significantly augmented shikonin-caused glioma cell necrosis. Furthermore, pretreatment with MnTBAP prevented the shikonin-induced upregulation of RIP1 and RIP3 expression and their interaction while pretreatment with rotenone reinforced these effects. These findings suggest that ROS is not only an executioner of shikonin-induced glioma cell necrosis but also a regulator of RIP1 and RIP3 expression and necrosome assembly.

Indexed as

AnimalsAntineoplastic AgentsApoptosisBrain NeoplasmsCell Line, TumorDose-Response Relationship, DrugGliomaHumansMitochondriaNaphthoquinonesNecrosisNuclear Pore Complex ProteinsOxidative StressProtein Serine-Threonine KinasesRatsReactive Oxygen SpeciesAGFG1 protein, humanAntineoplastic AgentsNaphthoquinonesNuclear Pore Complex ProteinsProtein Serine-Threonine KinasesReactive Oxygen SpeciesReceptor-Interacting Protein Serine-Threonine KinasesRIPK1 protein, ratRIPK3 protein, humanRipk3 protein, ratRNA-Binding Proteinsshikonin

Identifiers

PMID28816233
PMCPMC5672068
OpenAlexW2745337591

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.