Cancer Cell Biology

Serenoa repens (Permixon®) inhibits the 5 -reductase activity of human prostate cancer cell lines without interfering with PSA expression

Fouad K. Habib 1 * , Margaret Ross 1 , Clement K.H. Ho 1 , Valerie Lyons 2 , Karen Chapman 2

1Prostate Research Group, University of Edinburgh, School of Molecular and Clinical Medicine, Western General Hospital, Edinburgh, UK
2Endocrinology Unit, Molecular Medicine Centre, University of Edinburgh, School of Molecular and Clinical Medicine, Western General Hospital, Edinburgh, UK

The authors certify that they have not entered into any agreement that could interfere with their access to the data on the research or their ability to analyse the data independently, to prepare manuscripts and to publish them.

Funded by:
  Pierre Fabre Medicament

Keywords: phytotherapy • prostate cancer • transcriptional activity • androgen receptor-responsive genes

 

Abstract

The phytotherapeutic agent Serenoa repens is an effective dual inhibitor of 5 -reductase isoenzyme activity in the prostate. Unlike other 5 -reductase inhibitors, Serenoa repens induces its effects without interfering with the cellular capacity to secrete PSA. Here, we focussed on the possible pathways that might differentiate the action of Permixon from that of synthetic 5 -reductase inhibitors. We demonstrate that Serenoa repens, unlike other 5 -reductase inhibitors, does not inhibit binding between activated AR and the steroid receptor-binding consensus in the promoter region of the PSA gene. This was shown by a combination of techniques: assessment of the effect of Permixon on androgen action in the LNCaP prostate cancer cell line revealed no suppression of AR and maintenance of PSA protein expression at control levels. This was consistent with reporter gene experiments showing that Permixon failed to interfere with AR-mediated transcriptional activation of PSA and that both testosterone and DHT were equally effective at maintaining this activity. Our results demonstrate that despite Serenoa repens effective inhibition of 5 -reductase activity in the prostate, it did not suppress PSA secretion. Therefore, we confirm the therapeutic advantage of Serenoa repens over other 5 -reductase inhibitors as treatment with the phytotherapeutic agent will permit the continuous use of PSA measurements as a useful biomarker for prostate cancer screening and for evaluating tumour progression. © 2004 Wiley-Liss, Inc.

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