Figure 9.

Schematic representation of the effects induced by Exe plus CBD in MCF-7aro cells. This combination compromises the binding of estrogens, produced by aromatase, to ERα, decreasing ERα protein levels and the transcription of some ERα-targeted genes, including EGR3. The reduction in EGR3 levels inhibits the activation of ERK_1/2 signaling pathway, which prevents the inhibition of pro-caspase-8, that is converted to caspase-8, and, together with caspase-9, activates caspase-7, promoting apoptosis. Moreover, the effects of the combination on ERα modulate AR through an unknown crosstalk, contributing to the decreased EGR3 levels, avoiding the estrogen-like effect. Exe: Exemestane; CBD: cannabidiol; A: androstenedione; E: estrogens; ARO: aromatase; ER: estrogen receptor; AR: androgen receptor.