Evidence map›Paper›PMID 26230090›Full record

ArticlePloS one2015

Withaferin A Induces Cell Death Selectively in Androgen-Independent Prostate Cancer Cells but Not in Normal Fibroblast Cells.

Yukihiro Nishikawa, Daisuke Okuzaki, Kohshiro Fukushima, Satomi Mukai, Shouichi Ohno, Yuki Ozaki, Norikazu Yabuta, Hiroshi Nojima

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
13.6field-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

33 citing papers in PubMed, 70 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Withaferin A and Celastrol Overwhelm Proteostasis.International journal of molecular sciences · 2023
    Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Pharmaceutics · 2022
    Review
  10. Frontiers in pharmacology · 2022
    Review
  11. Targeting TDP-43 Pathology Alleviates Cognitive and Motor Deficits Caused by Chronic Cerebral Hypoperfusion.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021
    Article
  12. Review
  13. Article
  14. A Perspective onJournal of immunology research · 2021
    Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. International journal of molecular sciences · 2019
    Review
  20. Article
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 1 institution in 1 country.

Yukihiro NishikawaDepartment of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita City, Osaka, 565-0871, Japan.
Daisuke OkuzakiDepartment of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita City, Osaka, 565-0871, Japan; DNA-chip Development Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita City, Osaka, 565-0871, Japan.
Kohshiro FukushimaDepartment of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita City, Osaka, 565-0871, Japan.
Satomi MukaiDepartment of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita City, Osaka, 565-0871, Japan.
Shouichi OhnoDepartment of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita City, Osaka, 565-0871, Japan.
Yuki OzakiDepartment of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita City, Osaka, 565-0871, Japan.
Norikazu YabutaDepartment of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita City, Osaka, 565-0871, Japan.
Hiroshi NojimaDepartment of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita City, Osaka, 565-0871, Japan; DNA-chip Development Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita City, Osaka, 565-0871, Japan.
Osaka University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Withaferin A (WA), a major bioactive component of the Indian herb Withania somnifera, induces cell death (apoptosis/necrosis) in multiple types of tumor cells, but the molecular mechanism underlying this cytotoxicity remains elusive. We report here that 2 μM WA induced cell death selectively in androgen-insensitive PC-3 and DU-145 prostate adenocarcinoma cells, whereas its toxicity was less severe in androgen-sensitive LNCaP prostate adenocarcinoma cells and normal human fibroblasts (TIG-1 and KD). WA also killed PC-3 cells in spheroid-forming medium. DNA microarray analysis revealed that WA significantly increased mRNA levels of c-Fos and 11 heat-shock proteins (HSPs) in PC-3 and DU-145, but not in LNCaP and TIG-1. Western analysis revealed increased expression of c-Fos and reduced expression of the anti-apoptotic protein c-FLIP(L). Expression of HSPs such as HSPA6 and Hsp70 was conspicuously elevated; however, because siRNA-mediated depletion of HSF-1, an HSP-inducing transcription factor, reduced PC-3 cell viability, it is likely that these heat-shock genes were involved in protecting against cell death. Moreover, WA induced generation of reactive oxygen species (ROS) in PC-3 and DU-145, but not in normal fibroblasts. Immunocytochemistry and immuno-electron microscopy revealed that WA disrupted the vimentin cytoskeleton, possibly inducing the ROS generation, c-Fos expression and c-FLIP(L) suppression. These observations suggest that multiple events followed by disruption of the vimentin cytoskeleton play pivotal roles in WA-mediated cell death.

Indexed as

AndrogensAutophagyCell DeathCell Line, TumorCulture Media, Serum-FreeDrug Resistance, NeoplasmEndoplasmic ReticulumFibroblastsGene Expression Regulation, NeoplasticHumansMaleMitochondriaProstatic NeoplasmsProto-Oncogene Proteins c-fosSubcellular FractionsUp-RegulationAndrogensCulture Media, Serum-FreeProto-Oncogene Proteins c-fosVimentinwithaferin AWithanolides

Identifiers

PMID26230090
PMCPMC4521694
OpenAlexW1922342700

What OpenQuestion holds

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Read underepoch 390

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.