ArticleBMC cancer2014
Reversible inhibition of lysine specific demethylase 1 is a novel anti-tumor strategy for poorly differentiated endometrial carcinoma.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- New perspective on epigenetic modification and immunotherapy in endometrial cancer.Clinical epigenetics · 2026Review
- Oxidative stress-mediated responses in endometrial cancer cells: contrasting effects of doxorubicin and menadione.Frontiers in physiology · 2026Article
- Molecular subtyping of endometrial carcinoma cell lines uncovers subtype-specific targetable vulnerabilities.NPJ precision oncology · 2025Article
- The histone demethylase dLsd1 regulates organ size by silencing transposable elements.Communications biology · 2025Article
- Lysine demethylase LSD1 is associated with stemness in EBV-positive B cell lymphoma.Scientific reports · 2024Article
- LSD1 promotes prostate cancer reprogramming by repressing TP53 signaling independently of its demethylase function.JCI insight · 2023Article
- A ciprofloxacin derivative with four mechanisms of action overcomes paclitaxel resistance in p53-mutant and MDR1 gene-expressing type II human endometrial cancer.Biomaterials · 2023Article
- Targeting LSD1 in tumor immunotherapy: rationale, challenges and potential.Frontiers in immunology · 2023Review
- KDM1A inhibition augments the efficacy of rapamycin for the treatment of endometrial cancer.Cancer letters · 2022Article
- Epigenetic Deregulation of Apoptosis in Cancers.Cancers · 2021Review
- Roles of lysine-specific demethylase 1 (LSD1) in homeostasis and diseases.Journal of biomedical science · 2021Review
- Targeting Epigenetic Regulators for Endometrial Cancer Therapy: Its Molecular Biology and Potential Clinical Applications.International journal of molecular sciences · 2021Review
- Histone Modifying Enzymes in Gynaecological Cancers.Cancers · 2021Review
- An organoid-based drug screening identified a menin-MLL inhibitor for endometrial cancer through regulating the HIF pathway.Cancer gene therapy · 2021Article
- Biological roles of LSD1 beyond its demethylase activity.Cellular and molecular life sciences : CMLS · 2020Review
- Review
- Identification of key genes and pathways between type I and type II endometrial cancer using bioinformatics analysis.Oncology letters · 2019Article
- Genome-wide ChIP-seq data with a transcriptome analysis reveals the groups of genes regulated by histone demethylase LSD1 inhibition in esophageal squamous cell carcinoma cells.Oncology letters · 2019Article
- Pharmacological Inhibition of LSD1 for Cancer Treatment.Molecules (Basel, Switzerland) · 2018Review
- Preclinical studies reveal that LSD1 inhibition results in tumor growth arrest in lung adenocarcinoma independently of driver mutations.Molecular oncology · 2018Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundEndometrial cancer is the most common gynecologic malignancy. Type II endometrial carcinoma is often poorly differentiated and patients diagnosed with Type II disease (~11%) are disproportionately represented in annual endometrial cancer deaths (48%). Recent genomic studies highlight mutations in chromatin regulators as drivers in Type II endometrial carcinoma tumorigenesis, suggesting the use of epigenetic targeted therapies could provide clinical benefit to these patients. We investigated the anti-tumor efficacy of the LSD1 inhibitor HCI2509 in two poorly differentiated Type II endometrial cancer cell lines AN3CA and KLE.
methodsThe effects of HCI2509 on viability, proliferation, anchorage-independent growth, global histone methylation, LSD1 target gene induction, cell cycle, caspase activation and TUNEL were assayed. KLE cells were used in an orthotopic xenograft model to assess the anti-tumor activity of HCI2509.
resultsBoth AN3CA and KLE cells were sensitive to HCI2509 treatment with IC50s near 500 nM for cell viability. Inhibition of LSD1 with HCI2509 caused decreased proliferation and anchorage independent growth in soft agar, elevated global histone methylation, and perturbed the cell cycle in both cell lines. These effects were largely dose-dependent. HCI2509 treatment also caused apoptotic cell death. Orthotopic implantation of KLE cells resulted in slow-growing and diffuse tumors throughout the abdomen. Tumor burden was distributed log-normally. Treatment with HCI2509 resulted 5/9 tumor regressions such that treatment and regressions were significantly associated (p=0.034).
conclusionsOur findings demonstrate the anti-cancer properties of the LSD1 inhibitor HCI2509 on poorly differentiated endometrial carcinoma cell lines, AN3CA and KLE. HCI2509 showed single-agent efficacy in orthotopic xenograft studies. Continued studies are needed to preclinically validate LSD1 inhibition as a therapeutic strategy for endometrial carcinoma.
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