ArticleBiology open2012
ABT-737 synergizes with Bortezomib to kill melanoma cells.
Article in Biology open, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- miR in melanoma development: miRNAs and acquired hallmarks of cancer in melanoma.Physiological genomics · 2013Pooled it
- The role of the ubiquitin-proteasome pathway in skin cancer development: 26S proteasome-activated NF-κB signal transduction.Cancer biology & therapy · 2021Article
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- A Novel Regimen for Treating Melanoma: MCL1 Inhibitors and Azacitidine.Pharmaceuticals (Basel, Switzerland) · 2021Article
- BCL2L10 Is Overexpressed in Melanoma Downstream of STAT3 and Promotes Cisplatin and ABT-737 Resistance.Cancers · 2020Article
- Mcl-1 Inhibitor Induces Cells Death in BRAF-Mutant Amelanotic Melanoma Trough GSH Depletion, DNA Damage and Cell Cycle Changes.Pathology oncology research : POR · 2020Article
- Article
- Modulation of stress and immune response by Amblyomin-X results in tumor cell death in a horse melanoma model.Scientific reports · 2020Article
- The Role of the BCL-2 Family of Proteins in HIV-1 Pathogenesis and Persistence.Clinical microbiology reviews · 2019Review
- BCL-XL and MCL-1 are the key BCL-2 family proteins in melanoma cell survival.Cell death & disease · 2019Article
- Lactacystin: first-in-class proteasome inhibitor still excelling and an exemplar for future antibiotic research.The Journal of antibiotics · 2019Review
- Analysis of determinants for in vitro resistance to the small molecule deubiquitinase inhibitor b-AP15.PloS one · 2019Article
- Proteasome inhibitors against amelanotic melanoma.Cell biology and toxicology · 2017Article
- Bcl‑2 associated athanogene 4 promotes proliferation, migration and invasion of gastric cancer cells.Molecular medicine reports · 2017Article
- Use of a MCL-1 inhibitor alone to de-bulk melanoma and in combination to kill melanoma initiating cells.Oncotarget · 2017Article
- Combining a GSI and BCL-2 inhibitor to overcome melanoma's resistance to current treatments.Oncotarget · 2016Article
- Erdr1 Suppresses Murine Melanoma Growth via Regulation of Apoptosis.International journal of molecular sciences · 2016Article
- Therapeutic interventions to disrupt the protein synthetic machinery in melanoma.Pigment cell & melanoma research · 2015Review
- Alternative Treatments For Melanoma: Targeting BCL-2 Family Members to De-Bulk and Kill Cancer Stem Cells.The Journal of investigative dermatology · 2015Review
- Combining a BCL2 inhibitor with the retinoid derivative fenretinide targets melanoma cells including melanoma initiating cells.The Journal of investigative dermatology · 2015Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The BH3 mimetic ABT-737 is a potent inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X(L), and Bcl-w. The Bcl-2 family modulates sensitivity to anticancer drugs in many cancers, including melanomas. In this study, we examined whether ABT-737 is effective in killing melanoma cells either alone or in combination with a proteasome inhibitor already in clinical use (Bortezomib) in vitro and in vivo, and further evaluated the mechanisms of action. Results showed that ABT-737 alone induced modest cytotoxicity in melanoma cells, but only at higher doses. Knock-down of the anti-apoptotic proteins Bcl-2, Bcl-X(L), or Mcl-1 with siRNAs demonstrated that Mcl-1 is the critical mediator of melanoma's resistance to ABT-737 treatment. However, ABT-737 displayed strong synergistic lethality when combined with Bortezomib. Immunoblot analyses demonstrated that Bortezomib increased expression of Noxa, a pro-apoptotic Bcl-2 member that antagonizes Mcl-1. Additionally, siRNA-mediated inhibition of Noxa expression protected melanoma cells from cytotoxicity induced by the combination treatment. These results demonstrate that Bortezomib synergizes with ABT-737 by neutralizing Mcl-1's function via increased levels of Noxa. In a xenograft mouse model, although drug doses were limited due to toxicity, ABT-737 or Bortezomib slowed melanoma tumor growth compared to the control, and the drug combination significantly decreased growth compared to either drug alone. These data imply that less toxic drugs fulfilling a function similar to Bortezomib to neutralize Mcl-1 are promising candidates for combination with ABT-737 for treating melanomas.
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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.