The anti-
tumor role and mechanisms of
Cannabidiol (CBD), a non-psychotropic
cannabinoid compound, are not well studied especially in
triple-negative breast cancer (TNBC). In the present study, we analyzed CBD's anti-tumorigenic activity against highly aggressive
breast cancer cell lines including TNBC subtype. We show here -for the first time-that CBD significantly inhibits
epidermal growth factor (
EGF)-induced proliferation and chemotaxis of
breast cancer cells. Further studies revealed that CBD inhibits
EGF-induced activation of EGFR, ERK, AKT and
NF-kB signaling pathways as well as MMP2 and MMP9 secretion. In addition, we demonstrated that CBD inhibits
tumor growth and
metastasis in different mouse model systems. Analysis of molecular mechanisms revealed that CBD significantly inhibits the recruitment of tumor-associated macrophages in primary
tumor stroma and secondary lung
metastases. Similarly, our in vitro studies showed a significant reduction in the number of migrated RAW 264.7 cells towards the
conditioned medium of CBD-treated
cancer cells. The
conditioned medium of CBD-treated
cancer cells also showed lower levels of
GM-CSF and CCL3
cytokines which are important for macrophage recruitment and activation. In summary, our study shows -for the first time-that CBD inhibits
breast cancer growth and
metastasis through novel mechanisms by inhibiting
EGF/EGFR signaling and modulating the tumor microenvironment. These results also indicate that CBD can be used as a novel therapeutic option to inhibit growth and
metastasis of highly aggressive
breast cancer subtypes including TNBC, which currently have limited therapeutic options and are associated with poor prognosis and low survival rates.