The alpha1-adrenergic receptor antagonist doxazosin inhibits EGFR and NF-kappaB signalling to induce breast cancer cell apoptosis.

The selective alpha(1)-adrenergic receptor antagonist doxazosin (dox) has been reported to inhibit prostate cancer proliferation. We now demonstrate that dox-treatment inhibits proliferation and induces apoptosis in breast cancer cells in vitro by mechanisms that do not wholly involve the alpha1-adrenergic receptor. Intriguingly, dox-treatment reduced phosphorylated EGFR expression, decreased pERK1/2 levels and decreased NF-kappaB, AP-1, SRE, E2F and CRE-mediated transcriptional activity. EGF- and TNFalpha treatment alone failed to block dox-mediated breast cancer apoptotic effects, but combination of EGF and TNFalpha treatments completely abrogated dox-induced breast cancer cell apoptosis, indicating doxazosin inhibits both EGFR and NF-kappaB signalling pathways to induce breast cancer cell apoptosis. Doxazosin is proposed as a possible novel medical therapy for breast cancer.