PRIMA-1Met induces myeloma cell death independent of p53 by impairing the GSH/ROS balance
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Key Points: Myeloma cells are highly sensitive to PRIMA-1Met, independent of p53. PRIMA-1Met induces myeloma cell death by impairing GSH/ROS balance.
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APR-246/MQ binds to and depletes cellular glutathione.
“In addition, APR-246/MQ binds to and depletes cellular glutathione16,17.”
From Inhibition of the glutaredoxin and thioredoxin systems and ribonucleotide reductase by mutant p53-targeting compound APR-246 (2018) · cites this paper as [17]
The Discussion and figure caption (page unavailable) report that PRIMA-1Met induces cellular GSH depletion. The Discussion suggests that GSH-MEE, a glutathione derivative, may directly interact with PRIMA-1Met, but does not establish that APR-246/MQ binds cellular glutathione. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAPR-246 (PRIMA-1Met) induces cell death in myeloma cells by GSH depletion.
“Thessoulin and colleagues have shown that APR-246 (PRIMA-1Met) induces cell death in myeloma cells by GSH depletion17.”
From Inhibition of the glutaredoxin and thioredoxin systems and ribonucleotide reductase by mutant p53-targeting compound APR-246 (2018) · cites this paper as [17]
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- Authors
- Tessoulin, B., Descamps, G., Moreau, P., Maïga, S., Lodé, L., Godon, C., Marionneau-Lambot, S., Oullier, T., Le Gouill, S., Amiot, M., & Pellat-Deceunynck, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Centre Hospitalier Universitaire de Nantes (FR)
- Plate-forme in vivo, Cancéropôle Grand Ouest, Nantes, France
- Cancéropôle Grand Ouest (FR)
- INSERM, Unité Mixte de Recherche 892, Nantes, France;
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2014-09-04
- Volume
- 124
- Issue
- 10
- Pages
- 1626-1636
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2020203596
- Cited by
- 166
- References
- 42
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 13 · 2023: 14 · 2022: 19 · 2021: 18 · 2020: 22 · 2019: 13 · 2018: 20 · 2017: 15 · 2016: 17 · 2015: 6 · 2014: 1
- FWCI
- 9.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Institut National Du Cancer
- Institute of Cancer Research
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- PRIMA-1MET, multiple myeloma, p53-independent apoptosis, glutathione depletion, reactive oxygen species, Noxa, drug resistance, combination therapy, xenograft models
- MeSH terms
- Animals, Antineoplastic Agents, Cells, Cultured, Female, Glutathione, Humans, Multiple Myeloma, Quinuclidines, Signal Transduction, Tumor Suppressor Protein p53, Mice, SCID, Cell Death, Apoptosis, Reactive Oxygen Species, Xenograft Model Antitumor Assays, Mice
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