ArticleCancer biology & therapy2012
OSU-03012 suppresses GRP78/BiP expression that causes PERK-dependent increases in tumor cell killing.
Article in Cancer biology & therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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.
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
35 citing papers in PubMed, 53 citations in OpenAlex.
- Review
- Review
- GRP78 Activity Moderation as a Therapeutic Treatment against Obesity.International journal of environmental research and public health · 2022Review
- Article
- Canine osteosarcoma cells exhibit basal accumulation of multiple chaperone proteins and are sensitive to small molecule inhibitors of GRP78 and heat shock protein function.Cell stress & chaperones · 2022Article
- AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group AInternational journal of molecular sciences · 2021Article
- Celecoxib Analogues for Cancer Treatment: An Update on OSU-03012 and 2,5-Dimethyl-Celecoxib.Biomolecules · 2021Review
- Article
- AR12 (OSU-03012) suppresses GRP78 expression and inhibits SARS-CoV-2 replication.Biochemical pharmacology · 2020Article
- Characterizing Cell Stress and GRP78 in Glioma to Enhance Tumor Treatment.Frontiers in oncology · 2020Review
- Unfolded Protein Response as a Therapeutic Target in Cardiovascular Disease.Current topics in medicinal chemistry · 2019Review
- Kinase inhibitors: look beyond the label on the bottle.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- The oncogenic neurotrophin receptor tropomyosin-related kinase variant, TrkAIII.Journal of experimental & clinical cancer research : CR · 2018Review
- Role of the unfolded protein response in determining the fate of tumor cells and the promise of multi-targeted therapies.Cell stress & chaperones · 2018Review
- The convergent roles of NF-κB and ER stress in sunitinib-mediated expression of pro-tumorigenic cytokines and refractory phenotype in renal cell carcinoma.Cell death & disease · 2018Article
- Isochaihulactone-induced DDIT3 causes ER stress-PERK independent apoptosis in glioblastoma multiforme cells.Oncotarget · 2017Article
- Antileukemic Scalarane Sesterterpenoids and Meroditerpenoid from Carteriospongia (Phyllospongia) sp., Induce Apoptosis via Dual Inhibitory Effects on Topoisomerase II and Hsp90.Scientific reports · 2016Article
- AR-12 Inhibits Chaperone Proteins Preventing Virus Replication and the Accumulation of Toxic Misfolded Proteins.Journal of clinical & cellular immunology · 2016Article
- AR-12 Inhibits Multiple Chaperones Concomitant With Stimulating Autophagosome Formation Collectively Preventing Virus Replication.Journal of cellular physiology · 2016Article
- Multi-kinase inhibitors interact with sildenafil and ERBB1/2/4 inhibitors to kill tumor cells in vitro and in vivo.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
We have further defined mechanism(s) by which the drug OSU-03012 (OSU) kills tumor cells. OSU lethality was suppressed by knock down of PERK and enhanced by knock down of ATF6 and IRE1α. OSU treatment suppressed expression of the chaperone, BiP/GRP78, and did so through reduced stability of the protein. Knock down of BiP/GRP78 further enhanced OSU lethality. Overexpression of BiP/GRP78 abolished OSU toxicity. Pre-treatment of cells with OSU enhanced radiosensitivity to a greater extent than concomitant or sequential drug treatment with radiation exposure. Expression of a mutant active p110 PI3K, or mutant active forms of the EGFR in GBM cells did not differentially suppress OSU killing. In contrast loss of PTEN function reduced OSU lethality, without altering AKT, p70 S6K or mTOR activity, or the drug's ability to radiosensitize GBM cells. Knock down of PTEN protected cells from OSU and radiation treatment whereas re-expression of PTEN facilitated drug lethality and radiosensitization. In a dose-dependent fashion OSU prolonged the survival of mice carrying GBM tumors and interacted with radiotherapy to further prolong survival. Collectively, our data show that reduced BiP/GRP78 levels play a key role in OSU-3012 toxicity in GBM cells, and that this drug has in vivo activity against an invasive primary human GBM isolate.
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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.