ArticleCell death & disease2012
Translation inhibitors induce cell death by multiple mechanisms and Mcl-1 reduction is only a minor contributor.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 68 citations in OpenAlex.
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- Therapy-induced senescence is a transient drug resistance mechanism in breast cancer.Molecular cancer · 2025Article
- Homoharringtonine enhances cytarabine-induced apoptosis in acute myeloid leukaemia by regulating the p38 MAPK/H2AX/Mcl-1 axis.BMC cancer · 2024Article
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- High expression of ABCF1 is an independent predictor of poor prognosis in bladder cancer.BMC urology · 2023Article
- Targeting the translational machinery in gastrointestinal stromal tumors (GIST): a new therapeutic vulnerability.Scientific reports · 2022Article
- Inhibition of Protein Synthesis Induced by CHK1 Inhibitors Discriminates Sensitive from Resistant Cancer Cells.ACS pharmacology & translational science · 2021Article
- Multi-kinase targeted therapy as a promising treatment strategy for ovarian tumors expressing sfRon receptor.Genes & cancer · 2020Article
- RITA requires eIF2α-dependent modulation of mRNA translation for its anti-cancer activity.Cell death & disease · 2019Article
- New Thalidomide-Resembling Dicarboximides Target ABC50 Protein and Show Antileukemic and Immunomodulatory Activities.Biomolecules · 2019Article
- Redox modifications of cysteine-containing proteins, cell cycle arrest and translation inhibition: Involvement in vitamin C-induced breast cancer cell death.Redox biology · 2019Article
- Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson's disease.Translational neurodegeneration · 2019Review
- UBXN2A enhances CHIP-mediated proteasomal degradation of oncoprotein mortalin-2 in cancer cells.Molecular oncology · 2018Article
- A Review of Omacetaxine: A Chronic Myeloid Leukemia Treatment Resurrected.Oncology and therapy · 2018Review
- Cross-talk between protein synthesis, energy metabolism and autophagy in cancer.Current opinion in genetics & development · 2018Review
- Essential role for Bim in mediating the apoptotic and antitumor activities of immunotoxins.Oncogene · 2017Article
- Deletion of eIF2β lysine stretches creates a dominant negative that affects the translation and proliferation in human cell line: A tool for arresting the cell growth.Cancer biology & therapy · 2017Article
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Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
There is significant interest in treating cancers by blocking protein synthesis, to which hematological malignancies seem particularly sensitive. The translation elongation inhibitor homoharringtonine (Omacetaxine mepesuccinate) is undergoing clinical trials for chronic myeloid leukemia, whereas the translation initiation inhibitor silvestrol has shown promise in mouse models of cancer. Precisely how these compounds induce cell death is unclear, but reduction in Mcl-1, a labile pro-survival Bcl-2 family member, has been proposed to constitute the critical event. Moreover, the contribution of translation inhibitors to neutropenia and lymphopenia has not been precisely defined. Herein, we demonstrate that primary B cells and neutrophils are highly sensitive to translation inhibitors, which trigger the Bax/Bak-mediated apoptotic pathway. However, contrary to expectations, reduction of Mcl-1 did not significantly enhance cytotoxicity of these compounds, suggesting that it does not have a principal role and cautions that strong correlations do not always signify causality. On the other hand, the killing of T lymphocytes was less dependent on Bax and Bak, indicating that translation inhibitors can also induce cell death via alternative mechanisms. Indeed, loss of clonogenic survival proved to be independent of the Bax/Bak-mediated apoptosis altogether. Our findings warn of potential toxicity as these translation inhibitors are cytotoxic to many differentiated non-cycling cells.
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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.