ArticleMolecular cancer research : MCR2010
Bortezomib sensitizes human renal cell carcinomas to TRAIL apoptosis through increased activation of caspase-8 in the death-inducing signaling complex.
Article in Molecular cancer research : MCR, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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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
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Pooled it
- Phase II open-label study of recombinant circularly permuted TRAIL as a single-agent treatment for relapsed or refractory multiple myeloma.Chinese journal of cancer · 2016Trial
- Review
- Differential molecular mechanisms of bortezomib sensitization to rhTRAIL in non-small cell lung cancer cell lines.Exploration of targeted anti-tumor therapy · 2025Article
- Rolapitant treats lung cancer by targeting deubiquitinase OTUD3.Cell communication and signaling : CCS · 2024Article
- Bortezomib in Combination with Physachenolide C Reduces the Tumorigenic Properties of KRASCancers · 2024Article
- Inflammatory Networks in Renal Cell Carcinoma.Cancers · 2023Review
- Apoptosis: aJournal for immunotherapy of cancer · 2023Review
- Review on Bortezomib Resistance in Multiple Myeloma and Potential Role of Emerging Technologies.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Bortezomib Sustains T Cell Function by Inducing miR-155-Mediated Downregulation of SOCS1 and SHIP1.Frontiers in immunology · 2021Article
- Mechanism and therapeutic prospect of resveratrol combined with TRAIL in the treatment of renal cell carcinoma.Cancer gene therapy · 2020Article
- Article
- Cell death-related molecules and biomarkers for renal cell carcinoma targeted therapy.Cancer cell international · 2019Review
- Synergistic apoptosis of human gastric cancer cells by bortezomib and TRAIL.International journal of medical sciences · 2019Article
- Maritoclax Enhances TRAIL-Induced Apoptosis via CHOP-Mediated Upregulation of DR5 and miR-708-Mediated Downregulation of cFLIP.Molecules (Basel, Switzerland) · 2018Article
- Cytotoxic and other withanolides from aeroponically grown Physalis philadelphica.Phytochemistry · 2018Article
- Drug repurposing screening identifies bortezomib and panobinostat as drugs targeting cancer associated fibroblasts (CAFs) by synergistic induction of apoptosis.Investigational new drugs · 2018Article
- Preclinical evaluation of antitumor activity of the proteasome inhibitor MLN2238 (ixazomib) in hepatocellular carcinoma cells.Cell death & disease · 2018Article
- Withanolides from Aeroponically Grown Physalis peruviana and Their Selective Cytotoxicity to Prostate Cancer and Renal Carcinoma Cells.Journal of natural products · 2017Article
- Bax/Bak-independent mitochondrial depolarization and reactive oxygen species induction by sorafenib overcome resistance to apoptosis in renal cell carcinoma.The Journal of biological chemistry · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Bortezomib (VELCADE) could sensitize certain human renal cell carcinoma (RCC) lines to the apoptotic effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Analysis of seven human RCC showed a clear increase in the sensitivity of four of the RCC to TRAIL cytotoxicity following bortezomib (5-20 nmol/L) treatment, whereas the remaining three remained resistant. Tumor cell death following sensitization had all the features of apoptosis. The enhanced antitumor activity of the bortezomib and TRAIL combination was confirmed in long-term (6 days) cancer cell outgrowth assays. The extent of proteasome inhibition by bortezomib in the various RCC was equivalent. Following bortezomib treatment, neither changes in the intracellular protein levels of various Bcl-2 and IAP family members, nor minor changes in expression of TRAIL receptors (DR4, DR5), correlated well with the sensitization or resistance of RCC to TRAIL-mediated apoptosis. However, enhanced procaspase-8 activation following bortezomib pretreatment and subsequent TRAIL exposure was only observed in the sensitized RCC in both cell extracts and death-inducing signaling complex immunoprecipitates. These data suggest that the molecular basis for bortezomib sensitization of RCC to TRAIL primarily involves early amplification of caspase-8 activity. In the absence of this increased caspase-8 activation, other bortezomib-induced changes are not sufficient to sensitize RCC to TRAIL-mediated apoptosis.
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Registered trials
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