Evidence map›Paper›PMID 33627137›Full record

ArticleCell communication and signaling : CCS2021

Inhibition of the Otub1/c-Maf axis by the herbal acevaltrate induces myeloma cell apoptosis.

Tong Sun, Yujia Xu, Zhuan Xu, Biyin Cao, Zubin Zhang, Qi Wang, Yan Kong, Xinliang Mao

Open access · goldAbstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

16 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
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  6. Review
  7. Article
  8. Rolapitant treats lung cancer by targeting deubiquitinase OTUD3.Cell communication and signaling : CCS · 2024
    Article
  9. Article
  10. Potential Otubain1 Inhibitor, an Approach for a Treatment against Breast Cancer.International journal of molecular and cellular medicine · 2024
    Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
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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

8 authors at 3 institutions in 1 country.

Tong Sun *Institute of Clinical Pharmacology, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People's Republic of China.
Yujia Xu *Department of Pharmacology, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.
Zhuan Xu *Department of Neurology, the First Affiliated Hospital of Soochow University, Suzhou, 215100, Jiangsu, People's Republic of China.
Biyin CaoDepartment of Pharmacology, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.
Zubin ZhangDepartment of Pharmacology, Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.
Qi WangInstitute of Clinical Pharmacology, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People's Republic of China. wangqi@gzucm.edu.cn.
Yan KongDepartment of Neurology, the First Affiliated Hospital of Soochow University, Suzhou, 215100, Jiangsu, People's Republic of China. kong0919@163.com.
Xinliang MaoInstitute of Clinical Pharmacology, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People's Republic of China. xinliangmao@gzhmu.edu.cn.
Soochow University · CNFirst Affiliated Hospital of Soochow University · CNGuangzhou University of Chinese Medicine · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe oncogenic transcript factor c-Maf is stabilized by the deubiquitinase Otub1 and promotes myeloma cell proliferation and confers to chemoresistance. Inhibition of the Otub1/c-Maf axis is a promising therapeutic target, but there are no inhibitors reported on this specific axis.

methodsA luciferase assay was applied to screen potential inhibitors of Otub1/c-Maf. Annexin V staining/flow cytometry was applied to evaluate cell apoptosis. Immunoprecipitation was applied to examine protein ubiquitination and interaction. Xenograft models in nude mice were used to evaluate anti-myeloma activity of AVT.

resultsAcevaltrate (AVT), isolated from Valeriana glechomifolia, was identified based on a bioactive screen against the Otub1/c-Maf/luciferase system. AVT disrupts the interaction of Otub1/c-Maf thus inhibiting Otub1 activity and leading to c-Maf polyubiquitination and subsequent degradation in proteasomes. Consistently, AVT inhibits c-Maf transcriptional activity and downregulates the expression of its target genes key for myeloma growth and survival. Moreover, AVT displays potent anti-myeloma activity by triggering myeloma cell apoptosis in vitro and impairing myeloma xenograft growth in vivo but presents no marked toxicity.

conclusionsThe natural product AVT inhibits the Otub1/c-Maf axis and displays potent anti-myeloma activity. Given its great safety and efficacy, AVT could be further developed for MM treatment. Video Abstract.

Indexed as

AnimalsAntineoplastic Agents, PhytogenicApoptosisCell LineCell SurvivalCysteine EndopeptidasesCysteine Proteinase InhibitorsFemaleHumansIridoidsMiceMice, Inbred BALB CMice, NudeMultiple MyelomaProto-Oncogene Proteins c-mafacevaltrateAntineoplastic Agents, PhytogenicCysteine EndopeptidasesCysteine Proteinase InhibitorsIridoidsMaf protein, mouseOtub1 protein, mouseProto-Oncogene Proteins c-mafAcevaltratec-mafMyelomaOtub1Valerian

Identifiers

PMID33627137
PMCPMC7905600
OpenAlexW3133277350

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.