ArticlePloS one2012
Vorinostat eliminates multicellular resistance of mesothelioma 3D spheroids via restoration of Noxa expression.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 34 citations in OpenAlex.
- Mcl-1 dependence predicts response to vorinostat and gemtuzumab ozogamicin in acute myeloid leukemia.Leukemia research · 2014Trial
- Clinical Perspectives and Novel Preclinical Models of Malignant Pleural Mesothelioma: A Critical Review.ACS pharmacology & translational science · 2024Review
- Selective Eradication of Colon Cancer Cells Harboring PI3K and/or MAPK Pathway Mutations in 3D Culture by Combined PI3K/AKT/mTOR Pathway and MEK Inhibition.International journal of molecular sciences · 2023Article
- Hypoxia-Inducible Factor-1: A Novel Therapeutic Target for the Management of Cancer, Drug Resistance, and Cancer-Related Pain.Cancers · 2022Review
- Organoids as a Model for Precision Medicine in Malignant Pleural Mesothelioma: Where Are We Today?Cancers · 2022Review
- Review
- The Biology of Malignant Mesothelioma and the Relevance of Preclinical Models.Frontiers in oncology · 2020Review
- Proteasome stress sensitizes malignant pleural mesothelioma cells to bortezomib-induced apoptosis.Scientific reports · 2017Article
- Autophagy initiation correlates with the autophagic flux in 3D models of mesothelioma and with patient outcome.Autophagy · 2016Article
- Analysis of Gene Expression in 3D Spheroids Highlights a Survival Role for ASS1 in Mesothelioma.PloS one · 2016Article
- Resveratrol and clofarabine induces a preferential apoptosis-activating effect on malignant mesothelioma cells by Mcl-1 down-regulation and caspase-3 activation.BMB reports · 2015Article
- Autophagy Correlates with the Therapeutic Responsiveness of Malignant Pleural Mesothelioma in 3D Models.PloS one · 2015Article
- New histone deacetylase inhibitors improve cisplatin antitumor properties against thoracic cancer cells.Oncotarget · 2014Article
- Pazopanib and HDAC inhibitors interact to kill sarcoma cells.Cancer biology & therapy · 2014Article
- PIAS3 activates the intrinsic apoptotic pathway in non-small cell lung cancer cells independent of p53 status.International journal of cancer · 2014Article
- HDAC inhibitors enhance the lethality of low dose salinomycin in parental and stem-like GBM cells.Cancer biology & therapy · 2014Article
- Histone deacetylase inhibitors restore toxic BH3 domain protein expression in anoikis-resistant mammary and brain cancer stem cells, thereby enhancing the response to anti-ERBB1/ERBB2 therapy.Cancer biology & therapy · 2013Article
- Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
When grown in 3D cultures as spheroids, mesothelioma cells acquire a multicellular resistance to apoptosis that resembles that of solid tumors. We have previously found that resistance to the proteasome inhibitor bortezomib in 3D can be explained by a lack of upregulation of Noxa, the pro-apoptotic BH3 sensitizer that acts via displacement of the Bak/Bax-activator BH3-only protein, Bim. We hypothesized that the histone deacetylase inhibitor vorinostat might reverse this block to Noxa upregulation in 3D. Indeed, we found that vorinostat effectively restored upregulation of Noxa protein and message and abolished multicellular resistance to bortezomib in the 3D spheroids. The ability of vorinostat to reverse resistance was ablated by knockdown of Noxa or Bim, confirming the essential role of the Noxa/Bim axis in the response to vorinostat. Addition of vorinostat similarly increased the apoptotic response to bortezomib in another 3D model, the tumor fragment spheroid, which is grown from human mesothelioma ex vivo. In addition to its benefit when used with bortezomib, vorinostat also enhanced the response to cisplatin plus pemetrexed, as shown in both 3D models. Our results using clinically relevant 3D models show that the manipulation of the core apoptotic repertoire may improve the chemosensitivity of mesothelioma. Whereas neither vorinostat nor bortezomib alone has been clinically effective in mesothelioma, vorinostat may undermine chemoresistance to bortezomib and to other therapies thereby providing a rationale for combinatorial strategies.
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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.