ArticlePloS one2011
Stressing the ubiquitin-proteasome system without 20S proteolytic inhibition selectively kills cervical cancer cells.
Article in PloS one, 2011. 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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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
22 citing papers in PubMed, 38 citations in OpenAlex.
- Palmitoylethanolamide, an endogenous fatty acid amide, and its pleiotropic health benefits: A narrative review.Journal of biomedical research · 2024Article
- Chalcones as Promising Antitumor Agents by Targeting the p53 Pathway: An Overview and New Insights in Drug-Likeness.Molecules (Basel, Switzerland) · 2021Review
- Article
- Molecular and biological functions of gingerol as a natural effective therapeutic drug for cervical cancer.Journal of ovarian research · 2021Review
- Dienone Compounds: Targets and Pharmacological Responses.Journal of medicinal chemistry · 2020Article
- Physical and Functional Analysis of the Putative Rpn13 Inhibitor RA190.Cell chemical biology · 2020Article
- Drug Development Targeting the Ubiquitin-Proteasome System (UPS) for the Treatment of Human Cancers.Cancers · 2020Review
- GSK3β is a key regulator of the ROS-dependent necrotic death induced by the quinone DMNQ.Cell death & disease · 2020Article
- Structure-function analyses of candidate small molecule RPN13 inhibitors with antitumor properties.PloS one · 2020Article
- Small-Molecule Inhibitors of the Proteasome's Regulatory Particle.Chembiochem : a European journal of chemical biology · 2019Review
- UNC-45A Is a Novel Microtubule-Associated Protein and Regulator of Paclitaxel Sensitivity in Ovarian Cancer Cells.Molecular cancer research : MCR · 2019Article
- RNA Sequencing of Carboplatin- and Paclitaxel-Resistant Endometrial Cancer Cells Reveals New Stratification Markers and Molecular Targets for Cancer Treatment.Hormones & cancer · 2018Article
- Deubiquitinases and cancer: A snapshot.Critical reviews in oncology/hematology · 2016Review
- USP14 is a predictor of recurrence in endometrial cancer and a molecular target for endometrial cancer treatment.Oncotarget · 2016Article
- Proteasome inhibition mediates p53 reactivation and anti-cancer activity of 6-gingerol in cervical cancer cells.Oncotarget · 2015Article
- A reversible and highly selective inhibitor of the proteasomal ubiquitin receptor rpn13 is toxic to multiple myeloma cells.Journal of the American Chemical Society · 2015Article
- Simultaneous inhibition of deubiquitinating enzymes (DUBs) and autophagy synergistically kills breast cancer cells.Oncotarget · 2015Article
- Small-molecule RA-9 inhibits proteasome-associated DUBs and ovarian cancer in vitro and in vivo via exacerbating unfolded protein responses.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Cervical Cancer: Development of Targeted Therapies Beyond Molecular Pathogenesis.Current obstetrics and gynecology reports · 2014Article
- Molecular targeted approaches to cancer therapy and prevention using chalcones.Current cancer drug targets · 2014Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate, and for specific signaling pathways, notably HPV E6-targeted degradation of p53 and PDZ proteins. Natural compounds with antioxidant properties including flavonoids and triterpenoids hold promise as anticancer agents by interfering with ubiquitin-dependent protein degradation. An increasing body of evidence indicates that their α-β unsaturated carbonyl system is the molecular determinant for inhibition of ubiquitin-mediated protein degradation up-stream of the catalytic sites of the 20S proteasome. Herein we report the identification and characterization of a new class of chalcone-based, potent and cell permeable chemical inhibitors of ubiquitin-dependent protein degradation, and a lead compound RAMB1. RAMB1 inhibits ubiquitin-dependent protein degradation without compromising the catalytic activities of the 20S proteasome, a mechanism distinct from that of Bortezomib. Treatment of cervical cancer cells with RAMB1 triggers unfolded protein responses, including aggresome formation and Hsp90 stabilization, and increases p53 steady state levels. RAMB1 treatment results in activation of lysosomal-dependent degradation pathways as a mechanism to compensate for increasing levels of poly-ubiquitin enriched toxic aggregates. Importantly, RAMB1 synergistically triggers cell death of cervical cancer cells when combined with the lysosome inhibitor Chloroquine.
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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.