Investigational New Drugs

, Volume 28, Issue 6, pp 729–743 | Cite as

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

  • Maria Papaioannou
  • Sonja Schleich
  • Daniela Roell
  • Undine Schubert
  • Tamzin Tanner
  • Frank Claessens
  • Rudolf Matusch
  • Aria Baniahmad


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.


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



Human androgen receptor


Benign prostate hyperplasia


Cyproterone acetate


a LNCaP derivative cell line that exhibits androgen-independent growth


Kidney cell line from green monkey, lacking endogenously expressed functional AR, GR, ER, PR and TR


Dihydrotestosterone, androgen agonist




Human estrogen receptor


Glyceraldehyde-3-phosphate dehydrogenase


Green fluorescent protein


Human glucocorticoid receptor


Hormone binding domain


a human prostate cancer cell line, exhibits hormone-dependent growth


β-galactosidase expression vector used for normalization of transfection efficiency




Mouse mammary tumor virus




Hydroxyflutamide, androgen antagonist


Prostate cancer


a human prostate cancer cell line, lacking endogenously expressed functional AR


stable transfected PC3 cell line, expressing human wild type AR


Prostate specific antigen


Human progesterone receptor


Real time reverse transcription polymerase chain reaction


Methyltrienolone, androgen agonist


Relative light units (normalized to internal control)


Thyroid hormone (3,5,3′-triiodothyronine)


Thyroid hormone receptor


Two direct repeats as known TR response elements



We greatly thank Dr. O. Jänne, University of Helsinki, Finland, for providing the GFP-hAR expression plasmid.

Supplementary material

10637_2009_9304_MOESM1_ESM.ppt (326 kb)
Supplemental data (PPT 325 kb)


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Maria Papaioannou
    • 1
  • Sonja Schleich
    • 2
  • Daniela Roell
    • 1
  • Undine Schubert
    • 1
  • Tamzin Tanner
    • 3
  • Frank Claessens
    • 3
  • Rudolf Matusch
    • 2
  • Aria Baniahmad
    • 1
    • 4
  1. 1.Institute of Human GeneticsJena University HospitalJenaGermany
  2. 2.Institute for Pharmaceutical ChemistryPhilipps-University MarburgMarburgGermany
  3. 3.Division of Biochemistry, Faculty of MedicineUniversity of LeuvenLeuvenBelgium
  4. 4.Department of BiosciencesUniversity of KuopioKuopioFinland

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