Norcantharidin inhibits TOP2A expression via H3K27me3 mediated epigenetic regulation to alleviate the progression of hepatocellular carcinoma DOI Creative Commons
Ruibing Wu, Hailong Yuan, Yuehua Wang

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 3, 2025

Background Norcantharidin (NCTD), a bioactive compound derived from traditional Chinese medicine, has demonstrated promising anticancer activity against multiple malignancies, particularly hepatocellular carcinoma (HCC). However, its epigenetic regulatory mechanisms and associated transcriptional consequences remain poorly characterized. Methods In this study, we integrated biochemical assays with panel of cellular analyses assessing cell viability, proliferation, colony formation, migratory capacity to investigate NCTD’s therapeutic potential in HCC progression. Potential molecular targets NCTD were systematically identified through network pharmacology approaches. Chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) was performed quantify H3K27me3 enrichment level at the TOP2A locus NCTD-treated cells. Molecular docking simulations employed examine structural interactions between EZH2 (enhancer zeste homolog 2), while co-immunoprecipitation further conducted validate protein-protein protein phosphatase 1 (PP1). Results We topoisomerase IIα (TOP2A) as critical target mediating anti-HCC effects. Functional characterization revealed that significantly attenuated proliferation induced G2/M phase cycle arrest disruption TOP2A-p53 signaling axis. Mechanistic investigations epigenetically suppresses transcription via PRC2 (Polycomb Repressive Complex 2)-mediated deposition repressive histone mark promoter. Structural biology confirmed direct binding protein, consequently impairing PP1-mediated dephosphorylation enhancing complex stability. Conclusion Our findings establish exerts effects silencing TOP2A. This work not only elucidates novel pharmacoepigenetic mechanism underlying antitumor but also provides translational rationale for developing PRC2-targeted strategies management.

Язык: Английский

Norcantharidin inhibits TOP2A expression via H3K27me3 mediated epigenetic regulation to alleviate the progression of hepatocellular carcinoma DOI Creative Commons
Ruibing Wu, Hailong Yuan, Yuehua Wang

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 3, 2025

Background Norcantharidin (NCTD), a bioactive compound derived from traditional Chinese medicine, has demonstrated promising anticancer activity against multiple malignancies, particularly hepatocellular carcinoma (HCC). However, its epigenetic regulatory mechanisms and associated transcriptional consequences remain poorly characterized. Methods In this study, we integrated biochemical assays with panel of cellular analyses assessing cell viability, proliferation, colony formation, migratory capacity to investigate NCTD’s therapeutic potential in HCC progression. Potential molecular targets NCTD were systematically identified through network pharmacology approaches. Chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) was performed quantify H3K27me3 enrichment level at the TOP2A locus NCTD-treated cells. Molecular docking simulations employed examine structural interactions between EZH2 (enhancer zeste homolog 2), while co-immunoprecipitation further conducted validate protein-protein protein phosphatase 1 (PP1). Results We topoisomerase IIα (TOP2A) as critical target mediating anti-HCC effects. Functional characterization revealed that significantly attenuated proliferation induced G2/M phase cycle arrest disruption TOP2A-p53 signaling axis. Mechanistic investigations epigenetically suppresses transcription via PRC2 (Polycomb Repressive Complex 2)-mediated deposition repressive histone mark promoter. Structural biology confirmed direct binding protein, consequently impairing PP1-mediated dephosphorylation enhancing complex stability. Conclusion Our findings establish exerts effects silencing TOP2A. This work not only elucidates novel pharmacoepigenetic mechanism underlying antitumor but also provides translational rationale for developing PRC2-targeted strategies management.

Язык: Английский

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