ArticlePloS one2013
The HDAC inhibitor LBH589 induces ERK-dependent prometaphase arrest in prostate cancer via HDAC6 inactivation and down-regulation.
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 27 papers.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Screening anticancer peptides performance in organotypic prostate tumor-stroma 3D models.International journal of cancer · 2026Article
- Mechanism and application of feedback loops formed by mechanotransduction and histone modifications.Genes & diseases · 2024Review
- HDAC5 inhibition attenuates ventricular remodeling and cardiac dysfunction.Orphanet journal of rare diseases · 2023Article
- Inhibition of histone deacetylase 6 destabilizes ERK phosphorylation and suppresses cancer proliferation via modulation of the tubulin acetylation-GRP78 interaction.Journal of biomedical science · 2023Article
- HDAC6 regulates human erythroid differentiation through modulation of JAK2 signalling.Journal of cellular and molecular medicine · 2023Article
- HDAC6: A unique HDAC family member as a cancer target.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Evaluation of the Therapeutic Potential of Histone Deacetylase 6 Inhibitors for Primary and Metastatic Uveal Melanoma.International journal of molecular sciences · 2022Review
- Ricolinostat enhances adavosertib‑induced mitotic catastrophe in TP53‑mutated head and neck squamous cell carcinoma cells.International journal of oncology · 2022Article
- Uveal Melanoma Cell Line Proliferation Is Inhibited by Ricolinostat, a Histone Deacetylase Inhibitor.Cancers · 2022Article
- From Therapy Resistance to Targeted Therapies in Prostate Cancer.Frontiers in oncology · 2022Review
- Cytostatic Action of Novel Histone Deacetylase Inhibitors in Androgen Receptor-Null Prostate Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Development of an autophagy-related gene expression signature for prognosis prediction in prostate cancer patients.Journal of translational medicine · 2020Article
- Understanding Failure and Improving Treatment Using HDAC Inhibitors for Prostate Cancer.Biomedicines · 2020Review
- Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials.Science translational medicine · 2019Article
- Exploring Douglas-Peucker Algorithm in the Detection of Epileptic Seizure from Multicategory EEG Signals.BioMed research international · 2019Article
- 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
- Histone deacetylase 6 (HDAC6) deacetylates extracellular signal-regulated kinase 1 (ERK1) and thereby stimulates ERK1 activity.The Journal of biological chemistry · 2018Article
- GLP-1 treatment protects endothelial cells from oxidative stress-induced autophagy and endothelial dysfunction.International journal of biological sciences · 2018Article
- Valproic acid regulates Ang II-induced pericyte-myofibroblastAmerican journal of translational research · 2018Article
- Targeting HSP90-HDAC6 Regulating Network Implicates Precision Treatment of Breast Cancer.International journal of biological sciences · 2017Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone deacetylase inhibitors (HDACIs) have potent anti-cancer activity in a variety of cancer models. Understanding the molecular mechanisms involved in the therapeutic responsiveness of HDACI is needed before its clinical application. This study aimed to determine if a potent HDACI, LBH589 (Panobinostat), had differential therapeutic responsiveness towards LNCaP and PC-3 prostate cancer (PCa) cells. The former showed prometaphase arrest with subsequent apoptosis upon LBH589 treatment, while the latter was less sensitive and had late G2 arrest. The LBH589 treatment down-regulated HDAC6 and sustained ERK activation, and contributed to prometaphase arrest. Mechanistically, LBH589 inhibited HDAC6 activity, caused its dissociation from protein phosphatase PP1α, and increased 14-3-3ζ acetylation. Acetylated 14-3-3ζ released its mask effect on serine 259 of c-Raf and serine 216 of Cdc25C subsequent to de-phosphorylation by PP1α, which contributed to ERK activation. Enhanced ERK activity by LBH589 further down-regulated HDAC6 protein levels and sustained ERK activation by free-forward regulation. The sustained Cdc25C and ERK activation resulted in early M-phase (prometaphase) arrest and subsequent apoptosis in the most sensitive LNCaP cells but not in PC-3 cells. This study provides pre-clinical evidence that HDAC6 may serve as a sensitive therapeutic target in the treatment of prostate cancer with HDACI LBH589 for clinical translation. This study also posits a novel mechanism of HDAC6 participation in regulating the c-Raf-PP1-ERK signaling pathway and contributing to M phase cell-cycle transition.
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