ArticleMolecular cancer therapeutics2014
Regulation of OSU-03012 toxicity by ER stress proteins and ER stress-inducing drugs.
Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 34 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.
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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
34 citing papers in PubMed, 42 citations in OpenAlex.
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- Celecoxib Analogues for Cancer Treatment: An Update on OSU-03012 and 2,5-Dimethyl-Celecoxib.Biomolecules · 2021Review
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- Repurposing drugs in oncology (ReDO)-selective PDE5 inhibitors as anti-cancer agents.Ecancermedicalscience · 2018Article
- The celecoxib derivatives AR-12 and AR-14 induce autophagy and clear prion-infected cells from prions.Scientific reports · 2017Article
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- Beyond Alkylating Agents for Gliomas: Quo Vadimus?American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting · 2017Review
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Corrections and comments
- Expression of concern · 2019-09-03Duplication of/in Image ·
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The present studies examined the toxic interaction between the non-coxib celecoxib derivative OSU-03012 and phosphodiesterase 5 (PDE5) inhibitors, and also determined the roles of endoplasmic reticulum stress response regulators in cell survival. PDE5 inhibitors interacted in a greater than additive fashion with OSU-03012 to kill parental glioma and stem-like glioma cells. Knockdown of the endoplasmic reticulum stress response proteins IRE1 or XBP1 enhanced the lethality of OSU-03012, and of [OSU-03012 + PDE5 inhibitor] treatment. Pan-caspase and caspase-9 inhibition did not alter OSU-03012 lethality but did abolish enhanced killing in the absence of IRE1 or XBP1. Expression of the mitochondrial protective protein BCL-XL or the caspase-8 inhibitor c-FLIP-s, or knockdown of death receptor CD95 or the death receptor caspase-8 linker protein FADD, suppressed killing by [OSU-03012 + PDE5 inhibitor] treatment. CD95 activation was blocked by the nitric oxide synthase inhibitor L-NAME. Knockdown of the autophagy regulatory proteins Beclin1 or ATG5 protected the cells from OSU-03012 and from [OSU-03012 + PDE5 inhibitor] toxicity. Knockdown of IRE1 enhanced OSU-03012/[OSU-03012 + PDE5 inhibitor]-induced JNK activation, and inhibition of JNK suppressed the elevated killing caused by IRE1 knockdown. Knockdown of CD95 blunted JNK activation. Collectively, our data demonstrate that PDE5 inhibitors recruit death receptor signaling to enhance OSU-03012 toxicity in glioblastoma multiforme (GBM) cells.
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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.