Combination treatment of bicalutamide and curcumin has a strong therapeutic effect on androgen receptor-positive triple-negative breast cancers

Triple-negative breast cancers account for approximately 15-20% of breast cancer patients. Due to lack of expression of estrogen receptor, PR and human epidermal growth factor receptor 2 in triple-negative breast cancers, there are no targeted therapies available for these cancers. Therefore, a major research priority is to find potential therapeutic targets. Androgen receptor is present in 80-90% of all breast cancers, including 55% of estrogen receptor-alpha-negative cancers and 12%-35% of triple-negative breast cancers. Androgen receptor stimulates growth and survival in triple-negative breast cancer cells. Treatment with bicalutamide, an androgen receptor antagonist, has a good benefit for AR(+) triple-negative breast cancer patients. AR(+) triple-negative breast cancer cells were treated with curcumin or bicalutamide alone or in combination of both together. Cell growth, apoptosis and Wnt signaling pathways were examined. We found that curcumin dramatically suppressed Wnt signaling pathway in AR(+) triple-negative breast cancer cells. Curcumin treatment inhibited androgen receptor protein expression in AR(+) triple-negative breast cancer cells. Combination treatment of curcumin and bicalutamide has a robust increase in apoptosis. Furthermore, the combination treatment suppressed the growth of AR(+) triple-negative breast cancer cells more effectively than with the single drug alone. Our data indicate that androgen receptor inhibition is a potential therapeutic approach for AR(+) triple-negative breast cancers. In summary, our study for the first time shows that the combination treatment of curcumin and bicalutamide is effective in AR(+) triple-negative breast cancer cells.