ArticleBMC cancer2014
RITA (Reactivating p53 and Inducing Tumor Apoptosis) is efficient against TP53abnormal myeloma cells independently of the p53 pathway.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Therapeutic targeting of ARID1A-deficient cancer cells with RITA (Reactivating p53 and inducing tumor apoptosis).Cell death & disease · 2024Article
- Pathway-Directed Therapy in Multiple Myeloma.Cancers · 2021Review
- p53 CRISPR Deletion Affects DNA Structure and Nuclear Architecture.Journal of clinical medicine · 2020Article
- Targeting Oxidative Stress With Auranofin or Prima-1Frontiers in oncology · 2019Article
- Whole-exon sequencing of human myeloma cell lines shows mutations related to myeloma patients at relapse with major hits in the DNA regulation and repair pathways.Journal of hematology & oncology · 2018Article
- p53 regulates CD46 expression and measles virus infection in myeloma cells.Blood advances · 2018Article
- Deregulation and Targeting of TP53 Pathway in Multiple Myeloma.Frontiers in oncology · 2018Review
- Decitabine and Melphalan Fail to Reactivate p73 in p53 Deficient Myeloma Cells.International journal of molecular sciences · 2017Article
- RITA plus 3-MA overcomes chemoresistance of head and neck cancer cells via dual inhibition of autophagy and antioxidant systems.Redox biology · 2017Article
- Article
- Molecular Mechanisms of p53 Deregulation in Cancer: An Overview in Multiple Myeloma.International journal of molecular sciences · 2016Review
- Review
- Regulation of the DNA damage response by ubiquitin conjugation.Frontiers in genetics · 2015Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe aim of this study was to evaluate the efficacy of the p53-reactivating drugs RITA and nutlin3a in killing myeloma cells.
methodsA large cohort of myeloma cell lines (n = 32) and primary cells (n = 21) was used for this study. This cohort contained cell lines with various TP53 statuses and primary cells with various incidences of deletion of chromosome 17. Apoptosis was evaluated using flow cytometry with Apo2.7 staining of the cell lines or via the loss of the myeloma-specific marker CD138 in primary cells. Apoptosis was further confirmed by the appearance of a subG1 peak and the activation of caspases 3 and 9. Activation of the p53 pathway was monitored using immunoblotting via the expression of the p53 target genes p21, Noxa, Bax and DR5. The involvement of p53 was further studied in 4 different p53-silenced cell lines.
resultsBoth drugs induced the apoptosis of myeloma cells. The apoptosis that was induced by RITA was not related to the TP53 status of the cell lines or the del17p status of the primary samples (p = 0.52 and p = 0.80, respectively), and RITA did not commonly increase the expression level of p53 or p53 targets (Noxa, p21, Bax or DR5) in sensitive cells. Moreover, silencing of p53 in two TP53(mutated) cell lines failed to inhibit apoptosis that was induced by RITA, which confirmed that RITA-induced apoptosis in myeloma cells was p53 independent. In contrast, apoptosis induced by nutlin3a was directly linked to the TP53 status of the cell lines and primary samples (p < 0.001 and p = 0.034, respectively) and nutlin3a increased the level of p53 and p53 targets in a p53-dependent manner. Finally, we showed that a nutlin3a-induced DR5 increase (≥ 1.2-fold increase) was a specific and sensitive marker (p < 0.001) for a weak incidence of 17p deletion within the samples (≤ 19%).
conclusionThese data show that RITA, in contrast to nutlin3a, effectively induced apoptosis in a subset of MM cells independently of p53. The findings and could be of interest for patients with a 17p deletion, who are resistant to current therapies.
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