ArticleLeukemia2000
Protease inhibitor-induced apoptosis: accumulation of wt p53, p21WAF1/CIP1, and induction of apoptosis are independent markers of proteasome inhibition.
Article in Leukemia, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01484626 (An Open-Label Phase I/II Study of Bendamustine, Weekly Bortezomib, Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma), which is not on this map. Cited by 59 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
An Open-Label Phase I/II Study of Bendamustine, Weekly Bortezomib, Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma
Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 206 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Phase II trial of bortezomib plus doxorubicin in hepatocellular carcinoma (E6202): a trial of the Eastern Cooperative Oncology Group.Investigational new drugs · 2014Trial
- Trial
- Discovery of Autophagy Modulators that Increase I1061T NPC1 Expression and Promote Cholesterol Efflux in Niemann-Pick Type C Patient-Derived Fibroblasts.ACS chemical biology · 2026Article
- Dissecting Complex Interactions Between Ferroptosis and the Proteasome.bioRxiv : the preprint server for biology · 2026Article
- Structural Design, Anticancer Evaluation, and Molecular Docking of Newly Synthesized Ni(II) Complexes withMolecules (Basel, Switzerland) · 2024Article
- Modular Synthesis of Complex Benzoxaboraheterocycles through Chelation-Assisted Rh-Catalyzed [2 + 2 + 2] Cycloaddition.ACS catalysis · 2024Article
- Liposomes for Cancer Theranostics.Pharmaceutics · 2023Review
- Review
- Article
- Article
- Cordycepin induces Bax‑dependent apoptosis in colorectal cancer cells.Molecular medicine reports · 2019Article
- The first-in-class alkylating HDAC inhibitor EDO-S101 is highly synergistic with proteasome inhibition against multiple myeloma through activation of multiple pathways.Blood cancer journal · 2017Article
- Disulfiram overcomes bortezomib and cytarabine resistance in Down-syndrome-associated acute myeloid leukemia cells.Journal of experimental & clinical cancer research : CR · 2017Article
- Use of carfilzomib in second-line therapy and beyond for relapsed multiple myeloma.Blood and lymphatic cancer : targets and therapy · 2017Review
- Anti-leukemic activity of bortezomib and carfilzomib on B-cell precursor ALL cell lines.PloS one · 2017Article
- Bortezomib-resistance is associated with increased levels of proteasome subunits and apoptosis-avoidance.Oncotarget · 2016Article
- A Bowman-Birk inhibitor induces apoptosis in human breast adenocarcinoma through mitochondrial impairment and oxidative damage following proteasome 20S inhibition.Cell death discovery · 2016Article
- Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines.Cell death discovery · 2015Article
- Bortezomib induces AMPK-dependent autophagosome formation uncoupled from apoptosis in drug resistant cells.Oncotarget · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibitors of proteases are currently emerging as a potential anti-cancer modality. Nonselective protease inhibitors are cytotoxic to leukemia and cancer cell lines and we found that this cytotoxicity is correlated with their potency as inhibitors of the proteasome but not as inhibitors of calpain and cathepsin. Highly selective inhibitors of the proteasome were more cytotoxic and fast-acting than less selective inhibitors (PS341>>ALLN>>ALLM). Induction of wt p53 correlated with inhibition of the proteasome and antiproliferative effect in MCF7, a breast cancer cell line, which was resistant to apoptosis caused by proteasome inhibitors. In contrast, inhibitors of the proteasome induced apoptosis in four leukemia cell lines lacking wt p53. The order of sensitivity of leukemia cells was: Jurkat>HL60> or =U937>>K562. The highly selective proteasome inhibitor PS-341 induced cell death with an IC50 as low as 5 nM in apoptosis-prone leukemia cells. Cell death was preceded by p21WAF1/CIP1 accumulation, an alternative marker of proteasome inhibition, and by cleavage of PARP and Rb proteins and nuclear fragmentation. Inhibition of caspases abrogated PARP cleavage and nuclear fragmentation and delayed, but did not completely prevent cell death caused by PS-341. Reintroduction of wt p53 into p53-null PC3 prostate carcinoma cells did not increase their sensitivity to proteasome inhibitors. Likewise, comparison of parental and p21-deficient cells demonstrated that p21WAF1/CIP1 was dispensable for proteasome inhibitor-induced cytotoxicity. We conclude that accumulation of wt p53 and induction of apoptosis are independent markers of proteasome inhibition.
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What OpenQuestion holds
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.