ArticleCancer research2008
Oxidative stress plays a critical role in inactivating mutant BRAF by geldanamycin derivatives.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
- A multicenter phase II study of ganetespib monotherapy in patients with genotypically defined advanced non-small cell lung cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Trial
- Mechanistic Aspects of Inflammation and Oxidative Stress and Their Association With Thyroid Cancer Risk.Cancer medicine · 2025Review
- Reactive Oxygen Species and its Manipulation Strategies in Cancer Treatment.Current medicinal chemistry · 2025Review
- Targeting CRAF kinase in anti-cancer therapy: progress and opportunities.Molecular cancer · 2023Review
- 17-Aminogeldanamycin selectively diminishes IRE1α-XBP1s pathway activity and cooperatively induces apoptosis with MEK1/2 and BRAFApoptosis : an international journal on programmed cell death · 2019Article
- Apparent Lack ofFrontiers in immunology · 2019Article
- 17-AAG inhibits vemurafenib-associated MAP kinase activation and is synergistic with cellular immunotherapy in a murine melanoma model.PloS one · 2018Article
- Article
- Glucose-regulated protein 78 mediates the therapeutic efficacy of 17-DMAG in colon cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Expression of Hsp90α and cyclin B1 were related to prognosis of esophageal squamous cell carcinoma and keratin pearl formation.International journal of clinical and experimental pathology · 2014Article
- Oxidative inhibition of Hsp90 disrupts the super-chaperone complex and attenuates pancreatic adenocarcinoma in vitro and in vivo.International journal of cancer · 2013Article
- Oxidative stress: a new risk factor for thyroid cancer.Endocrine-related cancer · 2012Article
- Total oxidant/antioxidant status in sera of patients with thyroid cancers.Endocrine-related cancer · 2011Article
- Raf kinases in cancer-roles and therapeutic opportunities.Oncogene · 2011Review
- Differential impact of tetratricopeptide repeat proteins on the steroid hormone receptors.PloS one · 2010Article
- Withaferin A targets heat shock protein 90 in pancreatic cancer cells.Biochemical pharmacology · 2010Article
- Redox-directed cancer therapeutics: molecular mechanisms and opportunities.Antioxidants & redox signaling · 2009Review
- Antimelanoma activity of the redox dye DCPIP (2,6-dichlorophenolindophenol) is antagonized by NQO1.Biochemical pharmacology · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
The geldanamycin derivatives 17-allylamino-17-demethoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) are promising chemotherapeutic drugs that inhibit heat shock protein 90 (HSP90) function. Previous studies have shown that 17-AAG/DMAG treatment induces the degradation of mutant BRAF (V600E) and inhibits the activation of mitogen-activated protein/extracellular signal-regulated kinase 1/2 (MEK1/2). We have found, however, that HSP90 inhibition alone is not sufficient for efficient BRAF(V600E) degradation in some cells. HSP90 inhibitors structurally unrelated to geldanamycin, radicicol and novobiocin, while inducing the degradation of the HSP90 client protein RAF-1 fail to induce BRAF(V600E) degradation or inhibit MEK1/2 activation in HT29 human colon cancer cells. Moreover, after treatment with 17-DMAG, the kinase activity of residual, undegraded BRAF(V600E) was also lost. Incubation of cells with a reactive oxygen species (ROS) scavenger, N-acetyl cysteine, partially restored kinase activity and also partially prevented BRAF(V600E) degradation due to 17-DMAG treatment. Conversely, treatment with the ROS producing drug menadione clearly inhibited MEK1/2 and reduced BRAF(V600E). These results suggest that in addition to direct inhibition of HSP90, the antitumor effect of geldanamycin and its derivatives is also mediated though the production of ROS, which may directly inactivate tumorigenic mutant BRAF(V600E).
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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.