ArticleOncogene2003
The proteasome inhibitor PS-341 overcomes TRAIL resistance in Bax and caspase 9-negative or Bcl-xL overexpressing cells.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 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
58 citing papers in PubMed, 172 citations in OpenAlex.
- Differential molecular mechanisms of bortezomib sensitization to rhTRAIL in non-small cell lung cancer cell lines.Exploration of targeted anti-tumor therapy · 2025Article
- A Genome-Wide Loss-of-Function Screen Identifies SLC26A2 as a Novel Mediator of TRAIL Resistance.Molecular cancer research : MCR · 2017Article
- Journey of TRAIL from Bench to Bedside and its Potential Role in Immuno-Oncology.Oncology reviews · 2017Review
- Decursin enhances TRAIL-induced apoptosis through oxidative stress mediated- endoplasmic reticulum stress signalling in non-small cell lung cancers.British journal of pharmacology · 2016Article
- Bortezomib Improves Adoptive T-cell Therapy by Sensitizing Cancer Cells to FasL Cytotoxicity.Cancer research · 2015Article
- Trailing TRAIL Resistance: Novel Targets for TRAIL Sensitization in Cancer Cells.Frontiers in oncology · 2015Review
- Bortezomib sensitises TRAIL-resistant HPV-positive head and neck cancer cells to TRAIL through a caspase-dependent, E6-independent mechanism.Cell death & disease · 2014Article
- Regulation of TRAIL-receptor expression by the ubiquitin-proteasome system.International journal of molecular sciences · 2014Review
- The DeISGylase USP18 limits TRAIL-induced apoptosis through the regulation of TRAIL levels: Cellular levels of TRAIL influences responsiveness to TRAIL-induced apoptosis.Cancer biology & therapy · 2013Article
- Manipulating the apoptotic pathway: potential therapeutics for cancer patients.British journal of clinical pharmacology · 2013Review
- Modulating cell-to-cell variability and sensitivity to death ligands by co-drugging.Physical biology · 2013Article
- Bortezomib enhances antigen-specific cytotoxic T cell responses against immune-resistant cancer cells generated by STAT3-ablated dendritic cells.Pharmacological research · 2013Article
- Targeting death receptors: is this trail still hot?Translational pediatrics · 2013Article
- Oppositional regulation of Noxa by JNK1 and JNK2 during apoptosis induced by proteasomal inhibitors.PloS one · 2013Article
- BAK and NOXA are critical determinants of mitochondrial apoptosis induced by bortezomib in mesothelioma.PloS one · 2013Article
- Proteasome inhibition can impair caspase-8 activation upon submaximal stimulation of apoptotic tumor necrosis factor-related apoptosis inducing ligand (TRAIL) signaling.The Journal of biological chemistry · 2012Article
- Resistance to TRAIL and how to surmount it.Immunologic research · 2012Review
- Molecular targets of TRAIL-sensitizing agents in colorectal cancer.International journal of molecular sciences · 2012Review
- Inhibition of protein degradation induces apoptosis through a microtubule-associated protein 1 light chain 3-mediated activation of caspase-8 at intracellular membranes.Molecular and cellular biology · 2011Article
- Up-regulation of the DR5 expression by proteasome inhibitor MG132 augments TRAIL-induced apoptosis in soft tissue sarcoma cell lines.Cancer research and treatment · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We demonstrate that PS-341, a small molecule inhibitor of the proteasome, markedly sensitizes resistant prostate, colon, and bladder cancer cells to TNF-like apoptosis-inducing ligand (TRAIL)-induced apoptosis irrespective of Bcl-xL overexpression. PS-341 treatment by itself does not affect the levels of Bax, Bak, caspases 3 and 8, c-Flip or FADD, but elevates levels of TRAIL receptors DR4 and DR5. This increase in receptor protein levels is associated with the ubiquitination of the DR5 protein. When PS-341 is combined with TRAIL, the levels of activated caspase 8 and cleaved Bid are substantially increased. In Bax-negative TRAIL-resistant HC-4 colon cancer cells, the combination of PS-341 and TRAIL overcomes the block to activation of the mitochondrial pathway and causes SMAC and cytochrome c release followed by apoptosis. Similarly, murine embryonic fibroblasts lacking Bax undergo apoptosis when exposed to the combination of PS-341 and TRAIL; however, fibroblasts lacking Bak are significantly resistant. Taken together, these findings indicate that PS-341 enhances TRAIL-induced apoptosis by increasing the cleavage of caspase 8, causing Bak-dependent release of mitochondrial proapoptotic proteins.
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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.