ArticleFree radical biology & medicine2009
Role of oxidative stress in geldanamycin-induced cytotoxicity and disruption of Hsp90 signaling complex.
Article in Free radical biology & medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Disrupting the Hsp90-Cdc37 axis: a selective strategy for targeting oncogenic kinases in cancer.RSC advances · 2025Review
- Ferrocene thiazolidine-2,4-dione derivatives cause DNA damage and interfere with DNA repair in triple-negative breast cancer cells.PloS one · 2025Article
- Chaperone-mediated autophagy protects cardiomyocytes against hypoxic-cell death.American journal of physiology. Cell physiology · 2022Article
- Direct Interaction betweenAntioxidants (Basel, Switzerland) · 2022Review
- Genetically Modified Heat Shock Protein90s and Polyamine Oxidases inPlants (Basel, Switzerland) · 2019Article
- Methods to validate Hsp90 inhibitor specificity, to identify off-target effects, and to rethink approaches for further clinical development.Cell stress & chaperones · 2018Review
- Apoptosis in response to heat stress is positively associated with heat-shock protein 90 expression in chicken myocardial cellsJournal of veterinary science · 2017Article
- Fingerprinting of neurotoxic compounds using a mouse embryonic stem cell dual luminescence reporter assay.Archives of toxicology · 2017Article
- Stress Regulates Aquaporin-8 Permeability to Impact Cell Growth and Survival.Antioxidants & redox signaling · 2016Article
- Thioredoxin-1 redox signaling regulates cell survival in response to hyperoxia.Free radical biology & medicine · 2014Article
- Structure-activity relationship (SAR) of withanolides to inhibit Hsp90 for its activity in pancreatic cancer cells.Investigational new drugs · 2014Article
- Involvement of calcium-mediated reactive oxygen species in inductive GRP78 expression by geldanamycin in 9L rat brain tumor cells.International journal of molecular sciences · 2013Article
- Oxidative inhibition of Hsp90 disrupts the super-chaperone complex and attenuates pancreatic adenocarcinoma in vitro and in vivo.International journal of cancer · 2013Article
- Induction of apoptosis by luteolin involving akt inactivation in human 786-o renal cell carcinoma cells.Evidence-based complementary and alternative medicine : eCAM · 2013Article
- HSP90 inhibition by 17-DMAG reduces inflammation in J774 macrophages through suppression of Akt and nuclear factor-κB pathways.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2012Article
- Hsp90 is cleaved by reactive oxygen species at a highly conserved N-terminal amino acid motif.PloS one · 2012Article
- Article
- Celastrol targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent cytotoxicity in tumor cells.BMC cancer · 2011Article
- Differential impact of tetratricopeptide repeat proteins on the steroid hormone receptors.PloS one · 2010Article
- Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin inhibits the proliferation of ARPE-19 cells.Journal of biomedical science · 2010Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Heat shock protein 90 (Hsp90) is a chaperone protein regulating PC-12 cell survival by binding and stabilizing Akt, Raf-1, and Cdc37. Hsp90 inhibitor geldanamycin (GA) cytotoxicity has been attributed to the disruption of Hsp90 binding, and the contribution of oxidative stress generated by its quinone group has not been studied in this context. Reactive oxygen species (ROS) and cell survival were assessed in PC-12 cells exposed to GA or menadione (MEN), and Akt, Raf-1, and Cdc37 expression and binding to Hsp90 were determined. GA disrupted Hsp90 binding and increased ROS production starting at 1 h, and cell death occurred at 6 h, inhibited by N-acetylcysteine (NAC) without preventing dissociation of proteins. At 24 h, NAC prevented cytotoxicity and Hsp90 complex disruption. However, MnTBAP antioxidant treatment failed to inhibit GA cytotoxicity, suggesting that NAC acts by restoring glutathione. In contrast, 24 h MEN treatment induced cytotoxicity without disrupting Hsp90 binding. GA and MEN decreased Hsp90-binding protein expression, and proteasomal inhibition prevented MEN-, but not GA-induced degradation. In conclusion, whereas MEN cytotoxicity is mediated by ROS and proteasomal degradation, GA-induced cytotoxicity requires ROS but induces Hsp90 complex dissociation and proteasome-independent protein degradation. These differences between MEN- and GA-induced cytotoxicity may allow more specific targeting of cancer cells.
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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.