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

Toxicol In Vitro. 2023 Dec:93:105667. doi: 10.1016/j.tiv.2023.105667. Epub 2023 Aug 23.


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, Δ-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 suppressing the expression of the FAK, Akt, ERK1/2, p38MAPKs, and NF-κB upstream pathways, as well as inhibiting the Rac1/Cdc42 downstream pathways. In addition, CBD significantly inhibited the mTOR pathway. Furthermore, 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.

Keywords: Breast cancer; Cannabidiol; Cannabinoids; Invasion; Migration; Tetrahydrocannabinol.

MeSH terms

  • Apoptosis
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Cannabidiol* / pharmacology
  • Cannabinoids* / pharmacology
  • Cannabis* / metabolism
  • Female
  • Humans
  • MCF-7 Cells
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-akt


  • Cannabidiol
  • Cannabinoids
  • NF-kappa B
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases