Cannabidiol alters the epigenome of hormone-dependent prostate cancer cells.

Cosgrave J.; Magee R.; O'reilly E.; Hughes C.; Jordan A.; Silva R.; Mccabe A.; Dean K.; Prencipe M.; Gallagher W. et al. · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026

**Background & Methods** This in vitro study examined cannabidiol (CBD) effects on hormone-dependent prostate cancer cell lines (DU145, PC3, LNCaP) through multiple mechanistic approaches. Researchers assessed cell viability via MTT assay, analyzed transcriptomic changes using RNAseq and qRT-PCR, evaluated epigenetic modifications through methylation array analysis, and measured expression/activity of key epigenetic enzymes (DNMT1, EZH2) via Western blot and ELISA. **Key Findings** • **Epigenetic modulation**: CBD altered DNA methylation patterns in LNCaP cells and modulated DNMT1 and EZH2 expression across all three cell lines, though EZH2 catalytic activity remained unchanged, suggesting effects on enzyme expression rather than direct catalytic inhibition. • **Transcriptional changes**: CBD induced widespread gene expression alterations predominantly in LNCaP cells, with significant enrichment in cell cycle regulation pathways and downregulation of critical cell cycle regulators (CDK1/2), potentially explaining anti-proliferative effects. • **Anti-cancer efficacy and synergy**: CBD reduced prostate cancer cell viability in a dose-dependent manner and demonstrated additive or synergistic effects when combined with Talazoparib (PARP inhibitor), GSK126 (EZH2 inhibitor), and enzalutamide (hormonal therapy), suggesting therapeutic potential in combination strategies. **Dosage & Administration** The abstract does not specify the exact CBD concentrations tested or provide clinical dosing recommendations. Only that "varying concentrations of CBD" were administered to cell cultures. **Safety & Adverse Effects** Not reported. This was an in vitro cell culture study with no adverse event data applicable to clinical use. **Evidence Quality** This review-type study is limited by its preclinical nature, relying exclusively on cultured cell line models without animal or human validation. Cell line-based findings may not translate to in vivo biological systems where pharmacokinetics, metabolism, and immune interactions differ substantially. The study provides mechanistic insights but represents low-level evidence (in vitro data only). Differential responses across cell lines (stronger effects in LNCaP) suggest cell context-dependency. Lack of specificity regarding CBD concentrations limits reproducibility and clinical translatability. Further preclinical validation in animal models and eventual human trials would be necessary to support clinical therapeutic claims.

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