ArticleCell death & disease2020
Raloxifene prevents stress granule dissolution, impairs translational control and promotes cell death during hypoxia in glioblastoma cells.
Article in Cell death & disease, 2020. 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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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Raloxifene suppresses growth and promotes intrinsic apoptotic signaling in C6 glioma cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The assembly of stress granules during foot-and-mouth disease virus infection is uncoupled from activation of cellular intrinsic antiviral signalling.PLoS pathogens · 2026Article
- Estradiol and Raloxifene Protect Ovariectomized Mice from Acute Kidney Injury via G Protein-Coupled Estrogen Receptor-Mediated Nuclear Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Activation.International journal of molecular sciences · 2026Article
- Hypoxic stress granules trigger immunogenic dormancy in lung cancer.bioRxiv : the preprint server for biology · 2026Article
- Modulation of stress granules by lobeline increases cell death in hypoxia and impacts the ability of glioblastoma cells to secrete extracellular vesicles.Cell death discovery · 2025Article
- Stress granules promote quiescence by enhancing p21 levels and reducing phospho-Rb.RNA (New York, N.Y.) · 2025Article
- Review
- Stress granule formation is regulated by signaling machinery involving Sch9/Ypk1, sphingolipids, and Ubi4.Theranostics · 2025Article
- Review
- Altering biomolecular condensates as a potential mechanism that mediates cannabidiol effect on glioblastoma.Medical oncology (Northwood, London, England) · 2024Article
- Estrogen α and β Receptor Expression in the Various Regions of Resected Glioblastoma Multiforme Tumors and in an In Vitro Model.International journal of molecular sciences · 2024Article
- Protein aggregation and biomolecular condensation in hypoxic environments (Review).International journal of molecular medicine · 2024Review
- The role of PKN1 in glioma pathogenesis and the antiglioma effect of raloxifene targeting PKN1.Journal of cellular and molecular medicine · 2023Article
- Molecular signature to predict quality of life and survival with glioblastoma using Multiview omics model.PloS one · 2023Article
- ZBTB7A suppresses glioblastoma tumorigenesis through the transcriptional repression of EPB41L5.Experimental & molecular medicine · 2023Article
- Stress granules dynamics: benefits in cancer.BMB reports · 2022Review
- Article
- Tas2R activation relaxes airway smooth muscle by release of GαProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mechanism and effect of stress granule formation in cancer and its potential roles in breast cancer therapy.Genes & diseases · 2022Review
- Construction and Verification of a Novel Pyroptosis-Related lncRNA Signature Associated with Immune Landscape in Gliomas.Journal of oncology · 2022Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma (GBM) is the most common primary malignant brain tumor, and it has a uniformly poor prognosis. Hypoxia is a feature of the GBM microenvironment, and previous work has shown that cancer cells residing in hypoxic regions resist treatment. Hypoxia can trigger the formation of stress granules (SGs), sites of mRNA triage that promote cell survival. A screen of 1120 FDA-approved drugs identified 129 candidates that delayed the dissolution of hypoxia-induced SGs following a return to normoxia. Amongst these candidates, the selective estrogen receptor modulator (SERM) raloxifene delayed SG dissolution in a dose-dependent manner. SG dissolution typically occurs by 15 min post-hypoxia, however pre-treatment of immortalized U251 and U3024 primary GBM cells with raloxifene prevented SG dissolution for up to 2 h. During this raloxifene-induced delay in SG dissolution, translational silencing was sustained, eIF2α remained phosphorylated and mTOR remained inactive. Despite its well-described role as a SERM, raloxifene-mediated delay in SG dissolution was unaffected by co-administration of β-estradiol, nor did β-estradiol alone have any effect on SGs. Importantly, the combination of raloxifene and hypoxia resulted in increased numbers of late apoptotic/necrotic cells. Raloxifene and hypoxia also demonstrated a block in late autophagy similar to the known autophagy inhibitor chloroquine (CQ). Genetic disruption of the SG-nucleating proteins G3BP1 and G3BP2 revealed that G3BP1 is required to sustain the raloxifene-mediated delay in SG dissolution. Together, these findings indicate that modulating the stress response can be used to exploit the hypoxic niche of GBM tumors, causing cell death by disrupting pro-survival stress responses and control of protein synthesis.
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