Androgen receptor (AR) is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. The main function of the androgen receptor is as a DNA-binding transcription factor that regulates gene expression. Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens. They act by blocking the androgen receptor (AR) and/or inhibiting or suppressing androgen production. Antiandrogens are used to treat an assortment of androgen-dependent conditions. In men, antiandrogens can be uesd in prostate cancer, and enlarged prostate.

Bicalutamide is an orally active non-steroidal androgen receptor (AR) antagonist with an IC50 of 160 nM.

Bicalutamide is an anti-androgen, which competes with androgens for binding AR. Moreover, Bicalutamide inhibits the growth of prostate cancer by binding to the androgen receptor rather than androgen. Bicalutamide has the potential for prostate cancer research. Furthermore, Bicalutamide also induces the apoptosis of prostate cancer cells. In LNCaP cells, Bicalutamide increases the protein levels of caspase 3. Therefore, Bicalutamide has an apoptotic effect on endoplasmic reticulum (ER)-stress via fodrin-mediated apoptosis in LNCaP cells. However, in the setting of castration-resistant prostate cancer (CRPC), Bicalutamide undergoes an antagonist-to-agonist switch, stimulating AR activity. In absence of R1881, Bicalutamide partially activates VP16-AR-mediated transcription, indicative of AR binding to DNA. In addition, in VCaP cells, Bicalutamide induces cell-proliferation in a dose-dependent manner. Besides, Bicalutamide (10 mg/kg; for 28 days) exhibits anti-tumor activity in prostate cancer mice model.

In summary, Bicalutamide is an anti-androgen that can be used for the study of prostate cancer.

[1] Jiyeong Lee, et al. Exp Biol Med (Maywood). 2018 Jun;243(10):843-851.
[2] Nicola J Clegg, et al. Cancer Res. 2012 Mar 15;72(6):1494-503.