ArticleMolecular medicine reports2019
Pharmacological inhibition of EZH2 combined with DNA‑damaging agents interferes with the DNA damage response in MM cells.
Article in Molecular medicine reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Radiotherapy resistance in glioblastoma: Mechanistic insights and novel therapeutic approaches (Review).International journal of oncology · 2026Review
- Phosphorylation-mediated disassembly of C-terminal binding protein 2 tetramer impedes epigenetic silencing of pluripotency in mouse embryonic stem cells.Nucleic acids research · 2024Article
- SAM-Competitive EZH2-Inhibitors Induce Platinum Resistance by EZH2-Independent Induction of ABC-Transporters.Cancers · 2023Article
- High-throughput approaches to uncover synergistic drug combinations in leukemia.SLAS discovery : advancing life sciences R & D · 2023Article
- Characterization of a castrate-resistant prostate cancer xenograft derived from a patient of West African ancestry.Prostate cancer and prostatic diseases · 2022Article
- Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer.Breast cancer research : BCR · 2022Article
- One Omics Approach Does Not Rule Them All: The Metabolome and the Epigenome Join Forces in Haematological Malignancies.Epigenomes · 2021Review
- Finding an easy way to harmonize: a review of advances in clinical research and combination strategies of EZH2 inhibitors.Clinical epigenetics · 2021Review
- EZH2 has a non-catalytic and PRC2-independent role in stabilizing DDB2 to promote nucleotide excision repair.Oncogene · 2020Article
- EZH2 abnormalities in lymphoid malignancies: underlying mechanisms and therapeutic implications.Journal of hematology & oncology · 2019Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enhancer of zeste homolog 2 (EZH2) serves a pivotal role in epigenetic silencing by acting as a histone methyltransferase. It has been confirmed that EZH2 overexpression occurs in different types of cancer and is involved in drug resistance, while it remains unclear how a DNA‑damaging event may promote EZH2 expression in multiple myeloma (MM) cells and how EZH2 influences its susceptibility to death in response to DNA‑damaging chemotherapy. The present study examined the impact of EZH2 inhibition on DNA damage‑induced apoptosis in MM cells and elucidated its underlying molecular mechanism. It was demonstrated that pharmacological inhibition of EZH2 sensitized MM cells to DNA‑damaging agents and promoted limited caspase‑dependent apoptosis. Mechanistically, targeting EZH2 with minimal toxic concentrations of a pharmacological inhibitor (GSK126) markedly weakened the accompanying increase in the histone trimethylation H3K27me3 and aggravated DNA damage response (DDR)‑associated apoptosis in vitro. These data preliminarily confirmed the underlying molecular mechanisms of interaction between histone methylation and the DDR in MM cells, forming the rationale for the combination regimen of EZH2 inhibitors with DNA‑damaging agents for the treatment of MM.
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