Cannabidiol (CBD) altered gene regulation in prostate cancer cells and enhanced the effects of several targeted and hormonal cancer treatments, according to a new study published in Biomedicine & Pharmacotherapy.
Researchers from University College Dublin and University College Cork examined CBD in three human prostate cancer cell lines, including hormone-dependent LNCaP cells and hormone-independent PC3 and DU145 cells. The study focused on whether CBD could influence the epigenome, which helps regulate gene activity, while also reducing cancer cell viability and improving responses to existing treatments.
CBD produced substantial changes in DNA methylation in hormone-dependent LNCaP cells, but not in the hormone-independent PC3 and DU145 cells. Researchers identified hundreds of thousands of significantly altered methylation sites, with strong hypermethylation occurring more than twice as often as hypomethylation.
CBD also altered gene expression across all three prostate cancer cell lines. The treatment affected 353 genes in DU145 cells, 3,337 in PC3 cells and 5,468 in LNCaP cells. Among the pathways most consistently suppressed were those involved in DNA replication, cell division and the cell cycle. Key cell-cycle regulators including CDK1 and CDK2 were downregulated.
Researchers also found that CBD lowered expression of EZH2, a protein involved in epigenetic regulation and prostate cancer progression, across all three cell lines. In hormone-dependent cells, CBD reduced expression of several genes controlled by androgen receptor signaling, including KLK3, KLK2 and TMPRSS2.
Some of the strongest findings came when CBD was combined with existing cancer treatments.
Adding CBD to the EZH2 inhibitor GSK126 reduced PC3 cell viability by an additional 16.35% compared with GSK126 alone. In DU145 cells carrying a BRCA1 mutation, combining CBD with the PARP inhibitor talazoparib produced a further 24% reduction in cell viability compared with talazoparib alone.
The largest effect was observed with enzalutamide, a hormonal treatment used for prostate cancer. Combining 9.79 micromolar CBD with 14.02 micromolar enzalutamide reduced LNCaP cell viability to approximately 23% of untreated controls, representing a 54% reduction relative to enzalutamide alone. The researchers described the interaction as synergistic.
The authors conclude by stating “CBD exerts anti-cancer effects in prostate cancer, potentially through disruption of cell cycle regulation and epigenetic modulation. These findings support its potential as a therapeutic agent, particularly in combination with targeted treatments.”
