ArticlePloS one2017
Novel histone deacetylase inhibitor AR-42 exhibits antitumor activity in pancreatic cancer cells by affecting multiple biochemical pathways.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Tridax procumbens promotes apoptosis and suppresses markers of proliferation, growth, and metastasis in pancreatic ductal adenocarcinoma cells.BMC complementary medicine and therapies · 2026Article
- Non-alcoholic fatty pancreas disease (NAFPD) as a pre-neoplastic niche: Metabolic and inflammatory Gateways to pancreatic ductal adenocarcinoma.Journal of clinical & translational endocrinology · 2025Review
- Taming Pancreatic Cancer:International journal of medical sciences · 2025Article
- Towards simplified graph neural networks for identifying cancer driver genes in heterophilic networks.Briefings in bioinformatics · 2024Article
- Article
- The Breast Cancer Protooncogenes HER2, BRCA1 and BRCA2 and Their Regulation by the iNOS/NOS2 Axis.Antioxidants (Basel, Switzerland) · 2022Review
- Emerging epigenetic targets in rheumatoid arthritis.Rheumatology international · 2021Review
- A phase 1 trial of the histone deacetylase inhibitor AR-42 in patients with neurofibromatosis type 2-associated tumors and advanced solid malignancies.Cancer chemotherapy and pharmacology · 2021Article
- The Role of Epigenetics in the Progression of Clear Cell Renal Cell Carcinoma and the Basis for Future Epigenetic Treatments.Cancers · 2021Review
- Review
- AR-42: A Pan-HDAC Inhibitor with Antitumor and Antiangiogenic Activities in Esophageal Squamous Cell Carcinoma.Drug design, development and therapy · 2019Article
- Histone deacetylase inhibitor AR-42 inhibits breast cancer cell growth and demonstrates a synergistic effect in combination with 5-FU.Oncology letters · 2018Article
- Targeting Epigenetic Aberrations in Pancreatic Cancer, a New Path to Improve Patient Outcomes?Cancers · 2018Review
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Authors and funding
9 authors.
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Abstract
objectivePancreatic cancer is one of the most lethal types of cancer with a 5-year survival rate of ~5%. Histone deacetylases (HDACs) participate in many cellular processes, including carcinogenesis, and pharmacological inhibition of HDACs has emerged as a potential therapeutic strategy. In this study, we explored antitumor activity of the novel HDAC inhibitor AR-42 in pancreatic cancer.
methodsHuman pancreatic cancer cell lines BxPC-3 and PANC-1 were used in this study. Real-time PCR, RT-PCR, and western blotting were employed to investigate expression of specific genes and proteins, respectively. Translocation of apoptosis-inducing factor was investigated by immunofluorescence and subcellular fractionation. The number of apoptotic cells, cell cycle stages, and reactive oxygen species (ROS) generation levels were determined by flow cytometry. Cell invasiveness was examined by the Matrigel invasion assay. Efficacy of AR-42 in vivo was evaluated by utilizing BxPC-3 xenograft mouse model.
resultsAR-42 inhibited pancreatic cancer cell proliferation by causing G2/M cell cycle arrest via regulating expression levels of genes and proteins involved in cell cycle. AR-42 also induced ROS generation and DNA damage, triggering apoptosis of pancreatic cancer cells via both caspase-3-dependent and caspase-3-independent pathways. In addition, AR-42 increased expression levels of negative regulators of p53 (miR-125b, miR-30d, and miR33), which could contribute to lower expression level of mutant p53 in pancreatic cancer cells. Cell invasion assay showed that AR-42 reduced cancer cell aggressiveness and significantly diminished BxPC-3 xenograft tumor growth in vivo.
conclusionAR-42, a novel HDAC inhibitor, inhibited pancreatic cancer cells by regulating p53 expression, inducing cell cycle arrest, particularly at the G2/M stage, and activating multiple apoptosis pathways. Additionally, AR-42 inhibited cell invasiveness and potently suppressed pancreatic cancer tumors in vivo. We conclude that by virtue of its multiple mechanisms of action, AR-42 possesses a considerable potential as an antitumor agent in pancreatic cancer.
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