ArticleCell death & disease2012
Synergistic effects of nelfinavir and bortezomib on proteotoxic death of NSCLC and multiple myeloma cells.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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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.
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
46 citing papers in PubMed, 72 citations in OpenAlex.
- Nelfinavir triggers ferroptosis by inducing ER stress mediated downregulation of GPX4/GSH system, upregulation of NRF2/HO-1 axis, and mitochondrial impairment in hepatocellular carcinoma cells.Cell death discovery · 2025Article
- Mechanistic Insights and Therapeutic Potentials of Ubiquitin-Proteasome System in Non-Small Cell Lung Cancer.Cell proliferation · 2025Review
- Progress in ubiquitination and hepatocellular carcinoma: a bibliometric analysis.Discover oncology · 2025Article
- Significance of mouse xenograft tumor model using patient-derived cancer organoids for clinical drug development.Frontiers in oncology · 2025Article
- HIV-protease inhibitors potentiate the activity of carfilzomib in triple-negative breast cancer.British journal of cancer · 2024Article
- Discovering Potential in Non-Cancer Medications: A Promising Breakthrough for Multiple Myeloma Patients.Cancers · 2024Review
- Chemical Proteomics Reveals that the Anticancer Drug Everolimus Affects the Ubiquitin-Proteasome System.ACS pharmacology & translational science · 2024Article
- The cytotoxic activity of carfilzomib together with nelfinavir is superior to the bortezomib/nelfinavir combination in non-small cell lung carcinoma.Scientific reports · 2023Article
- Drug Repurposing in Non-Small Cell Lung Carcinoma: Old Solutions for New Problems.Current oncology (Toronto, Ont.) · 2023Review
- Viral proteases as therapeutic targets.Molecular aspects of medicine · 2022Review
- Review
- The aspartyl protease DDI2 drives adaptation to proteasome inhibition in multiple myeloma.Cell death & disease · 2022Article
- The roles of E3 ligases in Hepatocellular carcinoma.American journal of cancer research · 2022Review
- Article
- Treatment with HIV-Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma.Cancer research · 2021Article
- Review
- Review
- Article
- Bortezomib Inhibits Multiple Myeloma Cells by Transactivating ATF3 to Trigger miR-135a-5p- Dependent Apoptosis.Frontiers in oncology · 2021Article
- Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Exploiting protein homeostasis is a new therapeutic approach in cancer. Nelfinavir (NFV) is an HIV protease inhibitor that induces endoplasmic reticulum (ER) stress in cancer cells. Under conditions of ER stress, misfolded proteins are transported from the ER back to the cytosol for subsequent degradation by the ubiquitin-proteasome system. Bortezomib (BZ) is a proteasome inhibitor and interferes with degradation of misfolded proteins. Here, we show that NFV and BZ enhance proteotoxicity in non-small cell lung cancer (NSCLC) and multiple myeloma (MM) cells. The combination synergistically inhibited cell proliferation and induced cell death. Activating transcription factor (ATF)3 and CCAAT-enhancer binding protein homologous protein (CHOP), markers of ER stress, were rapidly increased, and their siRNA-mediated knockdown inhibited cell death. Knockdown of double-stranded RNA activated protein kinase-like ER kinase, a signal transducer in ER stress, significantly decreased apoptosis. Pretreatment with the protein synthesis inhibitor, cycloheximide, decreased levels of ubiquitinated proteins, ATF3, CHOP, and the overall total cell death, suggesting that inhibition of protein synthesis increases cell survival by relieving proteotoxic stress. The NFV/BZ combination inhibited the growth of NSCLC xenografts, which correlated with the induction of markers of ER stress and apoptosis. Collectively, these data show that NFV and BZ enhance proteotoxicity in NSCLC and MM cells, and suggest that this combination could tip the precarious balance of protein homeostasis in cancer cells for therapeutic gain.
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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.