ArticleCancer biology & therapy2009
Bcl-2 antagonists interact synergistically with bortezomib in DLBCL cells in association with JNK activation and induction of ER stress.
Article in Cancer biology & therapy, 2009. 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 It has been retracted, and should not be counted.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 17 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.
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
17 citing papers in PubMed, 36 citations in OpenAlex.
- ABT‑737 increases cisplatin sensitivity through the ROS‑ASK1‑JNK MAPK signaling axis in human ovarian cancer cisplatin‑resistant A2780/DDP cells.Oncology reports · 2024Article
- ER Stress Activates the NLRP3 Inflammasome: A Novel Mechanism of Atherosclerosis.Oxidative medicine and cellular longevity · 2019Review
- Mifepristone increases mRNA translation rate, triggers the unfolded protein response, increases autophagic flux, and kills ovarian cancer cells in combination with proteasome or lysosome inhibitors.Molecular oncology · 2016Article
- Bortezomib for the treatment of non-Hodgkin's lymphoma.Expert opinion on pharmacotherapy · 2014Review
- FADD the bad in head and neck cancer.Cancer biology & therapy · 2013Article
- The Bruton tyrosine kinase (BTK) inhibitor PCI-32765 synergistically increases proteasome inhibitor activity in diffuse large-B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells sensitive or resistant to bortezomib.British journal of haematology · 2013Article
- Deficiency of αB crystallin augments ER stress-induced apoptosis by enhancing mitochondrial dysfunction.Free radical biology & medicine · 2012Article
- 2-deoxyglucose-induced toxicity is regulated by Bcl-2 family members and is enhanced by antagonizing Bcl-2 in lymphoma cell lines.Oncogene · 2012Article
- Obatoclax interacts synergistically with the irreversible proteasome inhibitor carfilzomib in GC- and ABC-DLBCL cells in vitro and in vivo.Molecular cancer therapeutics · 2012Article
- ABT-737 induces Bim expression via JNK signaling pathway and its effect on the radiation sensitivity of HeLa cells.PloS one · 2012Article
- ER stress and apoptosis: a new mechanism for retinal cell death.Experimental diabetes research · 2012Review
- The expression of the endoplasmic reticulum stress sensor BiP/GRP78 predicts response to chemotherapy and determines the efficacy of proteasome inhibitors in diffuse large b-cell lymphoma.The American journal of pathology · 2011Article
- New strategies in diffuse large B-cell lymphoma: translating findings from gene expression analyses into clinical practice.Clinical cancer research : an official journal of the American Association for Cancer Research · 2011Review
- Potential usage of proteasome inhibitor bortezomib (Velcade, PS-341) in the treatment of metastatic melanoma: basic and clinical aspects.American journal of cancer research · 2011Article
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- AT-101, a small molecule inhibitor of anti-apoptotic Bcl-2 family members, activates the SAPK/JNK pathway and enhances radiation-induced apoptosis.Radiation oncology (London, England) · 2009Article
Corrections and comments
- Correction · 2019-05-22Duplication of/in Image · Falsification/Fabrication of Image · Investigation by Company/Institution · Investigation by ORI · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author · · Girija Dasmahapatra has ORI finding of research misconduct;
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Mechanisms underlying interactions between the proteasome inhibitor bortezomib and small molecule Bcl-2 antagonists were examined in GC- and ABC-type human DLBCL (diffuse lymphocytic B-cell lymphoma) cells. Concomitant or sequential exposure to non- or minimally toxic concentrations of bortezomib or other proteasome inhibitors and either HA14-1 or gossypol resulted in a striking increase in Bax/Bak conformational change/translocation, cytochrome c release, caspase activation and synergistic induction of apoptosis in both GC- and ABC-type cells. These events were associated with a sharp increase in activation of the stress kinase JNK and evidence of ER stress induction (e.g., eIF2alpha phosphorylation, activation of caspases-2 and -4, and Grp78 upregulation). Pharmacologic or genetic (e.g., shRNA knockdown) interruption of JNK signaling attenuated HA14-1/bortezomib lethality and ER stress induction. Genetic disruption of the ER stress pathway (e.g., in cells expressing caspase-4 shRNA or DN-eIF2alpha) significantly attenuated lethality. The toxicity of this regimen was independent of ROS generation. Finally, HA14-1 significantly increased bortezomib-mediated JNK activation, ER stress induction, and lethality in bortezomib-resistant cells. Collectively these findings indicate that small molecule Bcl-2 antagonists promote bortezomib-mediated mitochondrial injury and lethality in DLBCL cells in association with enhanced JNK activation and ER stress induction. They also raise the possibility that such a strategy may be effective in different DLBCL sub-types (e.g., GC- or ABC), and in bortezomib-resistant disease.
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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.