Author:

Keywords:

androgen receptor, prostate cancer, Science & Technology, Life Sciences & Biomedicine, Oncology, Pharmacology & Pharmacy, Antihormone, Prostate cancer, N-butylbenzene-sulfonamide, Natural compound, Pygeum africanum, Androgen receptor, THYROID-HORMONE-RECEPTOR, TRANSCRIPTION ACTIVATION, SCIENTIFIC BASIS, SERENOA-REPENS, LNCAP, EXPRESSION, BINDING, PROGRESSION, DIHYDROTESTOSTERONE, ANTIANDROGENS, Androgen Antagonists, Cell Line, Tumor, Cell Nucleus, Cell Proliferation, Humans, Ligands, Male, Phytotherapy, Plant Bark, Plant Extracts, Prostate-Specific Antigen, Prostatic Neoplasms, Protein Binding, Protein Structure, Tertiary, Protein Transport, Prunus africana, Receptors, Androgen, Receptors, Progesterone, Sulfonamides, Transcription, Genetic, 1115 Pharmacology and Pharmaceutical Sciences, Oncology & Carcinogenesis, 3211 Oncology and carcinogenesis, 3214 Pharmacology and pharmaceutical sciences

Abstract:

Extracts from Pygeum africanum are used in the treatment of prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The ligand-activated human androgen receptor (AR) is known to control the growth of the prostate gland. Inhibition of human AR is therefore a major goal in treatment of patients. Here, we characterize the compound N-butylbenzene-sulfonamide (NBBS) isolated from P. africanum as a specific AR antagonist. This antihormonal activity inhibits AR- and progesterone receptor- (PR) mediated transactivation, but not the related human glucocorticoid receptor (GR) or the estrogen receptors (ERα or ERβ). Importantly, NBBS inhibits both endogenous PSA expression and growth of human PCa cells. Mechanistically, NBBS binds to AR and inhibits its translocation to the cell nucleus. Furthermore, using a battery of chemically synthesized derivatives of NBBS we revealed important structural aspects for androgen antagonism and have identified more potent AR antagonistic compounds. Our data suggest that NBBS is one of the active compounds of P. africanum bark and may serve as a naturally occurring, novel therapeutic agent for treatment of prostatic diseases. Thus, NBBS and its derivatives may serve as novel chemical platform for treatment prostatitis, BPH and PCa.