Cannabinoids and standardized cannabis extracts inhibit migration, invasion, and induce apoptosis in MCF-7 cells through FAK/MAPK/Akt/ NF-KB signaling

Background: Breast cancer is the highest incidence of all types of cancer in women, and the cancer metastasis process accounts for a majority of cancer deaths. Two major cannabinoids, Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), from Cannabis sativa are expected to have anti-cancer activity. This study aimed to investigate the effects of THC, CBD, and standardized cannabis extracts (F1, F2, and F3) on migration, invasion, and apoptosis of human breast cancer (MCF-7) cells.Methods: Cell viability, survival, and apoptosis were determined using the MTT, clonogenic, and nuclear staining assays, respectively, while cancer cell migration and invasion were evaluated by the wound healing, trans-well, and filopodia assays. Western blot analysis was used to find out the mechanisms of the cannabinoids against MCF-7 cells.Results: CBD, THC, and F1 inhibited filopodia formation, migration, and invasion of MCF-7 cells through sup -pressing the expression of the FAK, Akt, ERK1/2, p38MAPKs, and NF -KB upstream pathways, as well as inhibiting the Rac1/Cdc42 downstream pathways. In addition, CBD significantly inhibited the mTOR pathway. Further-more, CBD and F1 induced apoptosis in MCF-7 cells via the Bcl-2/caspase-3 pathways. Conclusion: These results indicate that THC, CBD, and F1 have great abilities for preventing breast cancer cell metastasis in in vitro experiments.

Automated summary

The study demonstrated that CBD, THC, and standardized cannabis extracts have significant inhibitory effects on the migration, invasion, and apoptosis of breast cancer cells, mainly through regulation of multiple signaling pathways. CBD showed particular effectiveness in inhibiting the mTOR pathway and inducing apoptosis.