ArticleLeukemia2014
BIM upregulation and ROS-dependent necroptosis mediate the antitumor effects of the HDACi Givinostat and Sorafenib in Hodgkin lymphoma cell line xenografts.
Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 62 citations in OpenAlex.
- Reactive Oxygen Species: A Double-Edged Sword in the Modulation of Cancer Signaling Pathway Dynamics.Cells · 2025Review
- Chidamide and venetoclax synergistically regulate the Wnt/β-catenin pathway by MYCN/DKK3 in B-ALL.Annals of hematology · 2025Article
- Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.Molecular cancer · 2024Review
- Article
- Determinants for Antitumor and Protumor Effects of Programmed Cell Death.Cancer immunology research · 2024Article
- Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer.Molecular cancer · 2023Review
- Recent advancement of HDAC inhibitors against breast cancer.Medical oncology (Northwood, London, England) · 2023Review
- Cell death, therapeutics, and the immune response in cancer.Trends in cancer · 2023Review
- Monitoring Changes in Intracellular Reactive Oxygen Species Levels in Response to Histone Deacetylase Inhibitors.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The regulation of necroptosis and perspectives for the development of new drugs preventing ischemic/reperfusion of cardiac injury.Apoptosis : an international journal on programmed cell death · 2022Review
- Chidamide and venetoclax synergistically exert cytotoxicity on multiple myeloma by upregulating BIM expression.Clinical epigenetics · 2022Article
- KRAS and RAS-MAPK Pathway Deregulation in Mature B Cell Lymphoproliferative Disorders.Cancers · 2022Review
- Identification and Assessment of Necroptosis-Related Genes in Clinical Prognosis and Immune Cells in Diffuse Large B-Cell Lymphoma.Frontiers in oncology · 2022Article
- Potential Mechanism Underlying Exercise Upregulated Circulating Blood Exosome miR-215-5p to Prevent Necroptosis of Neuronal Cells and a Model for Early Diagnosis of Alzheimer's Disease.Frontiers in aging neuroscience · 2022Article
- Ethaselen synergizes with oxaliplatin in tumor growth inhibition by inducing ROS production and inhibiting TrxR1 activity in gastric cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- HSP90α Mediates Sorafenib Resistance in Human Hepatocellular Carcinoma by Necroptosis Inhibition under Hypoxia.Cancers · 2021Article
- Combined Anti-Cancer Effects of Platycodin D and Sorafenib on Androgen-Independent and PTEN-Deficient Prostate Cancer.Frontiers in oncology · 2021Article
- Treatment With the CSF1R Antagonist GW2580, Sensitizes Microglia to Reactive Oxygen Species.Frontiers in immunology · 2021Article
- Targeting necroptosis in anticancer therapy: mechanisms and modulators.Acta pharmaceutica Sinica. B · 2020Review
- Sorafenib sensitizes melanoma cells to vemurafenib through ferroptosis.Translational cancer research · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Relapsed/refractory Hodgkin's lymphoma (HL) is an unmet medical need requiring new therapeutic options. Interactions between the histone deacetylase inhibitor Givinostat and the RAF/MEK/ERK inhibitor Sorafenib were examined in HDLM-2 and L-540 HL cell lines. Exposure to Givinostat/Sorafenib induced a synergistic inhibition of cell growth (range, 70-80%) and a marked increase in cell death (up to 96%) due to increased H3 and H4 acetylation and strong mitochondrial injury. Gene expression profiling indicated that the synergistic effects of Givinostat/Sorafenib treatment are associated with the modulation of cell cycle and cell death pathways. Exposure to Givinostat/Sorafenib resulted in sustained production of reactive oxygen species (ROS) and activation of necroptotic cell death. The necroptosis inhibitor Necrostatin-1 prevented Givinostat/Sorafenib-induced ROS production, mitochondrial injury, activation of BH3-only protein BIM and cell death. Knockdown experiments identified BIM as a key signaling molecule that mediates Givinostat/Sorafenib-induced oxidative death of HL cells. Furthermore, in vivo xenograft studies demonstrated a 50% reduction in tumor burden (P<0.0001), a 5- to 15-fold increase in BIM expression (P < 0.0001) and a fourfold increase in tumor necrosis in Givinostat/Sorafenib-treated animals compared with mice that received single agents. These results provide a rationale for exploring Givinostat/Sorafenib combination in relapsed/refractory HL.
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Registered trials
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