ArticlePloS one2012
Withaferin A induces proteasome inhibition, endoplasmic reticulum stress, the heat shock response and acquisition of thermotolerance.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Targeting the proteasome in cancer therapy: development and future opportunities in natural products.Frontiers in pharmacology · 2026Review
- Article
- Review
- Withaferin A and Celastrol Overwhelm Proteostasis.International journal of molecular sciences · 2023Review
- A Redox-Silent Analogue of Tocotrienol May Break the Homeostasis of Proteasomes in Human Malignant Mesothelioma Cells by Inhibiting STAT3 and NRF1.International journal of molecular sciences · 2022Article
- A Pipeline for Natural Small Molecule Inhibitors of Endoplasmic Reticulum Stress.Frontiers in pharmacology · 2022Article
- Effect of Ashwagandha Withanolides on Muscle Cell Differentiation.Biomolecules · 2021Article
- Withaferin A Induces Heat Shock Response and Ameliorates Disease Progression in a Mouse Model of Huntington's Disease.Molecular neurobiology · 2021Article
- Role of Withaferin A and Its Derivatives in the Management of Alzheimer's Disease: Recent Trends and Future Perspectives.Molecules (Basel, Switzerland) · 2021Review
- Article
- Broad-spectrum antitumor properties of Withaferin A: a proteomic perspective.RSC medicinal chemistry · 2020Review
- The heat shock response in neurons and astroglia and its role in neurodegenerative diseases.Molecular neurodegeneration · 2017Review
- Protein Quality Control by Molecular Chaperones in Neurodegeneration.Frontiers in neuroscience · 2017Review
- Article
- AshwaMAX and Withaferin A inhibits gliomas in cellular and murine orthotopic models.Journal of neuro-oncology · 2016Article
- Withanolide E sensitizes renal carcinoma cells to TRAIL-induced apoptosis by increasing cFLIP degradation.Cell death & disease · 2015Article
- Withaferin A disrupts ubiquitin-based NEMO reorganization induced by canonical NF-κB signaling.Experimental cell research · 2015Article
- Withaferin A Induces Cell Death Selectively in Androgen-Independent Prostate Cancer Cells but Not in Normal Fibroblast Cells.PloS one · 2015Article
- Early-stage treatment with Withaferin A reduces levels of misfolded superoxide dismutase 1 and extends lifespan in a mouse model of amyotrophic lateral sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2015Article
- JNK-NQO1 axis drives TAp73-mediated tumor suppression upon oxidative and proteasomal stress.Cell death & disease · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the present study, withaferin A (WA), a steroidal lactone with anti-inflammatory and anti-tumor properties, inhibited proteasome activity and induced endoplasmic reticulum (ER) and cytoplasmic HSP accumulation in Xenopus laevis A6 kidney epithelial cells. Proteasomal inhibition by WA was indicated by an accumulation of ubiquitinated protein and a decrease in chymotrypsin-like activity. Additionally, immunoblot analysis revealed that treatment of cells with WA induced the accumulation of HSPs including ER chaperones, BiP and GRP94, as well as cytoplasmic/nuclear HSPs, HSP70 and HSP30. Furthermore, WA-induced an increase in the relative levels of the protein kinase, Akt, while the levels of actin were unchanged compared to control. Northern blot experiments determined that WA induced an accumulation in bip, hsp70 and hsp30 mRNA but not eIF-1α mRNA. Interestingly, WA acted synergistically with mild heat shock to enhance HSP70 and HSP30 accumulation to a greater extent than the sum of both stressors individually. This latter phenomenon was not observed with BiP or GRP94. Immunocytochemical analysis indicated that WA-induced BiP accumulation occurred mainly in the perinuclear region in a punctate pattern, while HSP30 accumulation occurred primarily in a granular pattern in the cytoplasm with some staining in the nucleus. Prolonged exposure to WA resulted in disorganization of the F-actin cytoskeleton as well as the production of relatively large HSP30 staining structures that co-localized with F-actin. Finally, prior exposure of cells to WA treatment, which induced the accumulation of HSPs conferred a state of thermal protection since it protected the F-actin cytoskeleton against a subsequent cytotoxic thermal challenge.
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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.