ArticlePloS one2019
Anti-tumor effects of the histone deacetylase inhibitor vorinostat on canine urothelial carcinoma cells.
Article in PloS one, 2019. 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, 39 citations in OpenAlex.
- Anti-tumor effect of a histone deacetylase inhibitor on canine malignant melanoma.The Journal of veterinary medical science · 2026Article
- Article
- Comparison of the Expression of Acetylated Histones H3 and H4 and the Deacetylase Enzymes HDACs 1, 2, and 6 in Neoplastic and Nonneoplastic Canine Mammary Tissues.Veterinary medicine international · 2025Article
- Comparative epigenomics to clinical trials in human breast cancer and canine mammary tumor.Animal cells and systems · 2025Review
- Anti-tumor effect of proteasome inhibitor on canine urothelial carcinoma.The Journal of veterinary medical science · 2024Article
- Stochasticity of anticancer mechanisms underlying clinical effectiveness of vorinostat.Heliyon · 2024Review
- Epigenetic regulation in muscle-invasive urothelial carcinoma of the bladder in the dog, a translational model of human cancer.Veterinary oncology (London, England) · 2024Article
- Discovery of novel polysubstitutedJournal of enzyme inhibition and medicinal chemistry · 2023Article
- Expression of acetylated histones H3 and H4 and histone deacetylase enzymes HDAC1, HDAC2 and HDAC6 in simple mammary carcinomas of female dogs.Frontiers in genetics · 2023Article
- Article
- Sorafenib inhibits tumor cell growth and angiogenesis in canine transitional cell carcinoma.The Journal of veterinary medical science · 2022Article
- Molecular Markers in Urinary Bladder Cancer: Applications for Diagnosis, Prognosis and Therapy.Veterinary sciences · 2022Review
- Detection of Canine Urothelial Carcinoma Cells in Urine Using 5-Aminolevulinic Acid.Animals : an open access journal from MDPI · 2022Article
- RNA-seq of nine canine prostate cancer cell lines reveals diverse therapeutic target signatures.Cancer cell international · 2022Article
- Anticancer Effect of Rh2, a Histone Deacetylase Inhibitor, in HepG2 Cells and HepG2 Cell-Derived Xenograft Tumors Occurs via the Inhibition of HDACs and Activation of the MAPK Signaling Pathway.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Trichostatin A promotes esophageal squamous cell carcinoma cell migration and EMT through BRD4/ERK1/2-dependent pathway.Cancer medicine · 2021Article
- Thiazolidinedione "Magic Bullets" Simultaneously Targeting PPARγ and HDACs: Design, Synthesis, and Investigations of theirJournal of medicinal chemistry · 2021Article
- The impact of damage-associated molecules released from canine tumor cells on gene expression in macrophages.Scientific reports · 2021Article
- Histone Deacetylase Inhibitors and Microtubule Inhibitors Induce Apoptosis in Feline Luminal Mammary Carcinoma Cells.Animals : an open access journal from MDPI · 2021Article
- Aberrant expression of the COX2/PGEScientific reports · 2020Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Canine urothelial carcinoma (cUC) is the most common tumor of the lower urinary tract in dogs. Although chemotherapy and radical surgery have improved the overall survival, most dogs with cUC succumb to metastasis or recurrence. Therefore, the development of an effective systematic therapy is warranted. In this study, a comprehensive drug screening test using a cUC cell line was performed and the anti-tumor effect of a histone deacetylase (HDAC) inhibitor was evaluated. Comprehensive drug screening was performed on cUC cells. Based on this screening, the anti-proliferation effect of vorinostat, an HDAC inhibitor clinically applied in humans, was evaluated using several cUC cell lines in sulforhodamine B and flow cytometry assays. Western blot analysis was also performed to evaluate the degree of acetylation of histone H3 as well as the expression and phosphorylation of cell cycle-related molecules. The anti-tumor effect of vorinostat in vivo was evaluated using a xenograft model. Finally, immunohistochemistry was performed on acetyl-histone H3 in cUC and the relationship between the degree of acetylation and prognosis was examined using Kaplan-Meier survival analysis. Drug screening revealed that HDAC inhibitors consistently inhibited the growth of cUC cells. Vorinostat inhibited the growth of 6 cUC cell lines in a dose-dependent manner and induced G0/G1 cell cycle arrest. Western blot analysis showed that vorinostat mediated the acetylation of histone H3, the dephosphorylation of p-Rb, and the upregulation of p21 upon exposure to vorinostat. Furthermore, inhibition of tumor growth was observed in the xenograft model. In clinical cUC cases, neoplastic urothelium showed significant deacetylation of histones compared to the normal control, where lower histone acetylation levels were associated with a poor prognosis. In conclusion, the therapeutic potential of vorinostat was demonstrated in cUC. Histone deacetylation may be related to cUC tumor progression.
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