ArticleBritish journal of cancer2011
Potentiation of apoptosis by histone deacetylase inhibitors and doxorubicin combination: cytoplasmic cathepsin B as a mediator of apoptosis in multiple myeloma.
Article in British journal of cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Meta analysis of bioactive compounds, miRNA, siRNA and cell death regulators as sensitizers to doxorubicin induced chemoresistance.Apoptosis : an international journal on programmed cell death · 2022Pooled it
- Trial
- Comparison of chemotherapy and chidamide combined with chemotherapy in patients with untreated angioimmunoblastic T-cell lymphoma.Frontiers in oncology · 2024Article
- IL6Myc mouse is an immunocompetent model for the development of aggressive multiple myeloma.Haematologica · 2023Article
- Intestinal Microbes and Hematological Malignancies.Cancers · 2023Review
- Comparison of Chemotherapy Combined With Chidamide Versus Chemotherapy in the Frontline Treatment for Peripheral T-Cell Lymphoma.Frontiers in immunology · 2022Article
- Predicting heterogeneity in clone-specific therapeutic vulnerabilities using single-cell transcriptomic signatures.Genome medicine · 2021Article
- Cysteinyl cathepsins in cardiovascular diseases.Biochimica et biophysica acta. Proteins and proteomics · 2020Review
- Effects of Intestinal Microbial⁻Elaborated Butyrate on Oncogenic Signaling Pathways.Nutrients · 2019Review
- Rutin and orlistat produce antitumor effects via antioxidant and apoptotic actions.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
- Cysteine protease cathepsins in cardiovascular disease: from basic research to clinical trials.Nature reviews. Cardiology · 2018Review
- AN-7, a butyric acid prodrug, sensitizes cutaneous T-cell lymphoma cell lines to doxorubicin via inhibition of DNA double strand breaks repair.Investigational new drugs · 2018Article
- Anticancer activity of salicin and fenofibrate.Naunyn-Schmiedeberg's archives of pharmacology · 2017Article
- Article
- Histone deacetylase inhibitors induce proteolysis of activated CDC42-associated kinase-1 in leukemic cells.Journal of cancer research and clinical oncology · 2016Article
- Cathepsin B Activity Initiates Apoptosis via Digestive Protease Activation in Pancreatic Acinar Cells and Experimental Pancreatitis.The Journal of biological chemistry · 2016Article
- Histone Deacetylase Inhibitors Enhance the Therapeutic Potential of Reovirus in Multiple Myeloma.Molecular cancer therapeutics · 2016Article
- Monitoring Tumor Response After Histone Deacetylase Inhibitor Treatment Using 3'-Deoxy-3'-[18F]-fluorothymidine PET.Molecular imaging and biology · 2015Article
- Lysosomal ceramide generated by acid sphingomyelinase triggers cytosolic cathepsin B-mediated degradation of X-linked inhibitor of apoptosis protein in natural killer/T lymphoma cell apoptosis.Cell death & disease · 2015Article
- Synergistic apoptotic response between valproic acid and fludarabine in chronic lymphocytic leukaemia (CLL) cells involves the lysosomal protease cathepsin B.Blood cancer journal · 2013Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough inhibitors of histone deacetylase inhibitors (HDACis) in combination with genotoxins potentiate apoptosis, the role of proteases other than caspases in this process remained elusive. Therefore, we examined the potentiation of apoptosis and related mechanisms of HDACis and doxorubicin combination in a panel of myeloma cell lines and in 25 primary myelomas.
resultsAt IC(50) concentrations, sodium butyrate (an HDACi) or doxorubicin alone caused little apoptosis. However, their combination potentiated apoptosis and synergistically reduced the viability of myeloma cells independent of p53 and caspase 3-7 activation. Potentiated apoptosis correlated with nuclear translocation of apoptosis-inducing factor, suggesting the induction of caspase 3- and 7-independent pathways. Consistent with this, butyrate and doxorubicin combination significantly increased the activity of cytoplasmic cathepsin B. Inhibition of cathepsin B either with a small-molecule inhibitor or downregulation with a siRNA reversed butyrate- and doxorubicin-potentiated apoptosis. Finally, ex vivo, clinically relevant concentrations of butyrate or SAHA (suberoylanilide hydroxamic acid, vorinostat, an HDACi in clinical testing) in combination with doxorubicin significantly (P<0.0001) reduced the survival of primary myeloma cells.
conclusionsCathepsin B has a prominent function in mediating apoptosis potentiated by HDACi and doxorubicin combinations in myeloma. Our results support a molecular model of lysosomal-mitochondrial crosstalk in HDACi- and doxorubicin-potentiated apoptosis through the activation of cathepsin B.
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