Evidence map›Paper›PMID 25452693›Full record

ArticleBiochemistry insights2014

Withaferin A Inhibits STAT3 and Induces Tumor Cell Death in Neuroblastoma and Multiple Myeloma.

Lisette P Yco, Gabor Mocz, John Opoku-Ansah, André S Bachmann

Registry-linked trialOpen access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochemistry insights, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07724873 (A Phase I/II Trial to Assess Safety and Activity of Standardized Withaferin A as GvHD Prophylaxis in Patients Undergoing Matched Related Donor Hematopoietic Stem Cell Transplant), which is not on this map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
7.9field-weighted citation impact, top 4% 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.

NCT07724873 phase1 / phase2recruitingnot on this mapstarted 2025, after this paper: background citation

A Phase I/II Trial to Assess Safety and Activity of Standardized Withaferin A as GvHD Prophylaxis in Patients Undergoing Matched Related Donor Hematopoietic Stem Cell Transplant

TypeinterventionalSponsorTata Memorial CentreRan2025 to 2029Enrolled54ConditionsHematopoietic Stem Cell Transplant (HSCT), GVHD - Graft-Versus-Host Disease, Hematological MalignancyArmsSWA (standardized root extract of Withania somnifera)
3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 41 citations in OpenAlex.

  1. Review
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  3. Frontiers in pharmacology · 2024
    Article
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  15. Article
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  17. Article
  18. Natural Withanolides in the Treatment of Chronic Diseases.Advances in experimental medicine and biology
    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

4 authors at 3 institutions in 1 country.

Lisette P YcoDepartment of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hilo, USA. ; Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu, Hawaii, USA.
Gabor MoczPacific Biosciences Research Center, University of Hawaii at Manoa, Honolulu, Hawaii, USA.
John Opoku-AnsahDepartment of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hilo, USA.
André S BachmannDepartment of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hilo, USA. ; Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu, Hawaii, USA. ; Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA. ; Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, USA.
University of Hawaii at Hilo · USMichigan State University · USUniversity of Hawaiʻi at Mānoa · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that has been implicated in many human cancers and has emerged as an ideal target for cancer therapy. Withaferin A (WFA) is a natural product with promising antiproliferative properties through its association with a number of molecular targets including STAT3. However, the effect of WFA in pediatric neuroblastoma (NB) and its interaction with STAT3 have not been reported. In this study, we found that WFA effectively induces dose-dependent cell death in high-risk and drug-resistant NB as well as multiple myeloma (MM) tumor cells, prevented interleukin-6 (IL-6)-mediated and persistently activated STAT3 phosphorylation at Y705, and blocked the transcriptional activity of STAT3. We further provide computational models that show that WFA binds STAT3 near the Y705 phospho-tyrosine residue of the STAT3 Src homology 2 (SH2) domain, suggesting that WFA prevents STAT3 dimer formation similar to BP-1-102, a well-established STAT3 inhibitor. Our findings propose that the antitumor activity of WFA is mediated at least in part through inhibition of STAT3 and provide a rationale for further drug development and clinical use in NB and MM.

Indexed as

molecular modelingmultiple myelomanatural productspediatric cancer neuroblastomasignal transducer and activator of transcription 3 (STAT3)Withaferin A (WFA)

Identifiers

PMID25452693
PMCPMC4226392
OpenAlexW2073369654

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.