CBD inhibited melanoma by activating a receptor that reprogrammed DNA methylation and turned on a tumor-suppressor gene

CBD induced apoptosis and inhibited proliferation and invasion of melanoma cells in vitro and reduced lung metastasis in vivo. The mechanism involved CBD activating PPARgamma, which formed a complex with TET1 (a demethylation enzyme). This complex removed methyl groups from the LRSAM1 gene promoter, activating this previously unrecognized anti-cancer gene. LRSAM1 upregulation enhanced melanoma cell death and suppressed proliferation.

In vitro studies with melanoma cell lines using MTS, EdU, Transwell invasion, and flow cytometry. In vivo murine lung metastasis model. Network pharmacology and molecular docking for target identification. Integrated transcriptomic and genome-wide methylation analyses. Co-immunoprecipitation and chromatin immunoprecipitation for protein interactions.

Melanoma is the most dangerous form of skin cancer, with limited treatment options for advanced stages. This study identifies a completely new molecular mechanism for CBD's anti-cancer effects and a previously unknown tumor-suppressor gene.

This represents a novel mechanism: CBD working through epigenetic reprogramming rather than direct cytotoxicity. The discovery of LRSAM1 as an anti-cancer gene could have implications beyond CBD, potentially informing other melanoma therapies.

Preclinical study with cell lines and mouse models. CBD concentrations used may not be achievable in humans. LRSAM1's role as a tumor suppressor needs independent confirmation. Melanoma is a heterogeneous cancer and results may not apply to all subtypes.