ArticleMedical oncology (Northwood, London, England)2021
The novel LSD1 inhibitor ZY0511 suppresses diffuse large B-cell lymphoma proliferation by inducing apoptosis and autophagy.
Article in Medical oncology (Northwood, London, England), 2021. 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, 18 citations in OpenAlex.
- Transcriptional and epigenetic regulation of autophagy: mechanisms, disease relevance and therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- The novel tertiary amine LSD1 inhibitor 596 inhibits endometrial cancer through the mTOR signal transduction pathway.Translational oncology · 2026Article
- Unlocking the Secrets of Regulated Cell Death in Large B-Cell Lymphoma Beyond Apoptosis: Signaling Pathways and Therapeutic Options.International journal of molecular sciences · 2026Review
- LC3 gene expression as a marker of autophagy in acute myeloid and lymphoblastic leukemia: a systematic review.Discover oncology · 2026Review
- Deubiquitinase TRIM44 Promotes Autophagy-Mediated Chemoresistance in Diffuse Large B Cell Lymphoma.Hematological oncology · 2025Article
- Epigenetic Symphony in Diffuse Large B-Cell Lymphoma: Orchestrating the Tumor Microenvironment.Biomedicines · 2025Review
- Histone demethylases in autophagy and inflammation.Cell communication and signaling : CCS · 2025Review
- Advances in epigenetic therapies for B-cell non-hodgkin lymphoma.Annals of hematology · 2024Review
- DLD is a potential therapeutic target for COVID-19 infection in diffuse large B-cell lymphoma patients.Apoptosis : an international journal on programmed cell death · 2024Article
- LSD1: an emerging face in altering the tumor microenvironment and enhancing immune checkpoint therapy.Journal of biomedical science · 2023Review
- Pharmacological inhibition of LSD1 suppresses growth of hepatocellular carcinoma by inducing GADD45B.MedComm · 2023Article
- Epigenetic Alterations in Canine Malignant Lymphoma: Future and Clinical Outcomes.Animals : an open access journal from MDPI · 2023Review
- The Status and Prospects of Epigenetics in the Treatment of Lymphoma.Frontiers in oncology · 2022Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Lysine-specific demethylase 1 (LSD1, also known as KDM1A) is an attractive agent for treatment of cancer. However, the anti-tumor effect of LSD1 inhibitors against diffuse large B-cell lymphoma (DLBCL) and the underlying mechanism are still unclear. Here, we report that KDM1A is overexpressed in human DLBCL tissues and negatively related to overall survival rate of DLBCL patients. ZY0511, a novel and potent LSD1 inhibitor developed by our group, inhibited the proliferation of human DLBCL cells. ZY0511 interacted with LSD1, induced methylation level of histone 3 lysine 4 and histone 3 lysine 9 in DLBCL cells. Mechanistically, transcriptome sequencing results indicated that ZY0511 induced the genes enrichment significantly related to cell cycle, autophagy, and apoptosis signaling pathways. Further study confirmed that ZY0511 blocked cell cycle at G0/G1 phase and expression of CDK4 and cyclin D1. ZY0511 decreased mitochondrial membrane potential and induced apoptosis, which can be reverted by a pan-caspase inhibitor, Z-VAD-FMK. Moreover, ZY0511 treatment significantly increased autophagy-associated marker proteins and autophagosomes formation in DLBCL cells. In vivo xenograft experiments confirmed that intraperitoneal administration of ZY0511 significantly suppressed SU-DHL-6 xenograft tumor growth in vivo. In conclusion, our findings identify that ZY0511 inhibits DLBCL growth both in vitro and in vivo via the induction of apoptosis and autophagy, and LSD1 inhibitor might be a promising strategy for treating DLBCL.
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