PRECLINICAL STUDIES

Investigational New Drugs

, Volume 28, Issue 6, pp 729-743

First online:

NBBS isolated from Pygeum africanum bark exhibits androgen antagonistic activity, inhibits AR nuclear translocation and prostate cancer cell growth

  • Maria PapaioannouAffiliated withInstitute of Human Genetics, Jena University Hospital
  • , Sonja SchleichAffiliated withInstitute for Pharmaceutical Chemistry, Philipps-University Marburg
  • , Daniela RoellAffiliated withInstitute of Human Genetics, Jena University Hospital
  • , Undine SchubertAffiliated withInstitute of Human Genetics, Jena University Hospital
  • , Tamzin TannerAffiliated withDivision of Biochemistry, Faculty of Medicine, University of Leuven
  • , Frank ClaessensAffiliated withDivision of Biochemistry, Faculty of Medicine, University of Leuven
  • , Rudolf MatuschAffiliated withInstitute for Pharmaceutical Chemistry, Philipps-University Marburg
  • , Aria BaniahmadAffiliated withInstitute of Human Genetics, Jena University HospitalDepartment of Biosciences, University of Kuopio Email author 

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Summary

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.

Keywords

Antihormone Prostate cancer N-butylbenzene-sulfonamide Natural compound Pygeum africanum Androgen receptor