ArticlePloS one2013
Panobinostat synergistically enhances the cytotoxic effects of cisplatin, doxorubicin or etoposide on high-risk neuroblastoma cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Epigallocatechin gallate enhances panobinostat-induced cytotoxicity through HDAC modulation in colorectal cancer cells.Molecular biology reports · 2026Article
- 3D genome organization shapes DNA damage susceptibility to platinum-based drugs.Nucleic acids research · 2025Article
- PHD-2/HIF-1α axis mediates doxorubicin-induced angiogenesis in SH-SY5Y neuroblastoma microenvironment: a potential survival mechanism.Scientific reports · 2025Article
- Recent Advances in Pineoblastoma Research: Molecular Classification, Modelling and Targetable Vulnerabilities.Cancers · 2025Review
- Article
- Doxorubicin-Induced TrkAIII Activation: A Selection Mechanism for Resistant Dormant Neuroblastoma Cells.International journal of molecular sciences · 2022Article
- Targeting Oncogenic Transcriptional Networks in Neuroblastoma: From N-Myc to Epigenetic Drugs.International journal of molecular sciences · 2021Review
- Neuroblastoma and the epigenome.Cancer metastasis reviews · 2021Review
- ACTL6A promotes repair of cisplatin-induced DNA damage, a new mechanism of platinum resistance in cancer.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy.Signal transduction and targeted therapy · 2020Review
- Understanding the Mechanisms by Which Epigenetic Modifiers Avert Therapy Resistance in Cancer.Frontiers in oncology · 2020Review
- Histone Deacetylases and Histone Deacetylase Inhibitors in Neuroblastoma.Frontiers in cell and developmental biology · 2020Review
- Carfilzomib enhances cisplatin-induced apoptosis in SK-N-BE(2)-M17 human neuroblastoma cells.Scientific reports · 2019Article
- Epigenetic regulation of neuroblastoma development.Cell and tissue research · 2018Review
- Targeting of epigenetic regulators in neuroblastoma.Experimental & molecular medicine · 2018Review
- Synergistic anticancer effect of panobinostat and topoisomerase inhibitors through ROS generation and intrinsic apoptotic pathway induction in cervical cancer cells.Cellular oncology (Dordrecht, Netherlands) · 2018Article
- The Histone Deacetylase Inhibitor Valproic Acid Exerts a Synergistic Cytotoxicity with the DNA-Damaging Drug Ellipticine in Neuroblastoma Cells.International journal of molecular sciences · 2018Article
- Identification and Testing of Novel CARP-1 Functional Mimetic Compounds as Inhibitors of Non-Small Cell Lung and Triple Negative Breast Cancers.Journal of biomedical nanotechnology · 2015Article
- The predictive value of ERCC1 and p53 for the effect of panobinostat and cisplatin combination treatment in NSCLC.Oncotarget · 2015Article
- Synergistic antitumor interactions between MK-1775 and panobinostat in preclinical models of pancreatic cancer.Cancer letters · 2015Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
High-risk neuroblastoma remains a therapeutic challenge with a long-term survival rate of less than 40%. Therefore, new agents are urgently needed to overcome chemotherapy resistance so as to improve the treatment outcome of this deadly disease. Histone deacetylase (HDAC) inhibitors (HDACIs) represent a novel class of anticancer drugs. Recent studies demonstrated that HDACIs can down-regulate the CHK1 pathway by which cancer cells can develop resistance to conventional chemotherapy drugs. This prompted our hypothesis that combining HDACIs with DNA damaging chemotherapeutic drugs for treating neuroblastoma would result in enhanced anti-tumor activities of these drugs. Treatment of high-risk neuroblastoma cell lines with a novel pan-HDACI, panobinostat (LBH589), resulted in dose-dependent growth arrest and apoptosis in 4 high-risk neuroblastoma cell lines. Further, the combination of panobinostat with cisplatin, doxorubicin, or etoposide resulted in highly synergistic antitumor interactions in the high-risk neuroblastoma cell lines, independent of the sequence of drug administration. This was accompanied by cooperative induction of apoptosis. Furthermore, panobinostat treatment resulted in substantial down-regulation of CHK1 and its downstream pathway and abrogation of the G2 cell cycle checkpoint. Synergistic antitumor interactions were also observed when the DNA damaging agents were combined with a CHK1-specific inhibitor, LY2603618. Contrary to panobinostat treatment, LY2603618 treatments neither resulted in abrogation of the G2 cell cycle checkpoint nor enhanced cisplatin, doxorubicin, or etoposide-induced apoptosis in the high-risk neuroblastoma cells. Surprisingly, LY2603618 treatments caused substantial down-regulation of total CDK1. Despite this discrepancy between panobinostat and LY2603618, our results indicate that suppression of the CHK1 pathway by panobinostat is at least partially responsible for the synergistic antitumor interactions between panobinostat and the DNA damaging agents in high-risk neuroblastoma cells. The results of this study provide a rationale for clinical evaluation of the combination of panobinostat and cisplatin, doxorubicin, or etoposide for treating children with high-risk neuroblastoma.
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Registered trials
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.