Influence of Rooibos on androgen metabolism in normal and cancer prostate cells – Prof Amanda Swart
Prof Amanda Swart
Title of the project
The influence of Rooibos on androgen metabolism in normal and cancer prostate cells.
In the prostate, androgens regulate cell growth and homeostasis, while also playing a central role in prostate cancer development. Androgens regulate growth by binding the androgen receptor (AR). The most potent active androgen reported to date, dihydrotestosterone (DHT) which is synthesized from testosterone (T), is closely linked to prostate cancer. Limiting the production of DHT is a major target in the treatment of prostate cancer as prostate cancer and benign prostatic hyperplasia (BPH) are both androgen dependent. Treatment includes inhibitors of androgen (T and DHT) production and anti-androgens which prevent DHT and other androgens from binding to the AR. Suppressing androgen production has been shown to lead to clinical improvement and lowered prostate specific antigen (PSA) plasma levels. Increased PSA is a well-established prostate cancer biomarker. The purpose of this study is to determine if Rooibos influences the production of adrenal C19 steroids which are converted to active androgens in the prostate. Rooibos may also influence the enzymes responsible for the formation of active androgens in the prostate as well as those enzymes catalyzing the inactivation of these androgens. The effect of Rooibos on PSA levels will also be determined.
This project has led to the identification and characterization of novel steroids which have to date been overlooked in prostate cancer treatment regimes. This has been published which is the first step in bringing it to the attention of the medical world and pharmaceutical companies. Furthermore, the researchers have identified additional steroids, the C11-oxy C21steroids, also produced in the adrenal gland, which may also be converted to potent androgens. The published reports have formed the groundwork Rooibos investigations, as the effects of Rooibos do need to be compared, in all cases, to effects obtained in assays conducted in the absence of Rooibos.
- Amanda C. Swart, Lindie Schloms, Karl-Heinz Storbeck, Liezl M. Bloem, Therina du Toit, Jonathan L. Quanson, William E. Rainey, Pieter Swart. 11β-Hydroxyandrostenedione, the product of androstenedione metabolism in the adrenal, is metabolized in LNCaP cells by 5α-reductase yielding 11 β -hydroxy-5α-androstanedione. Journal of Steroid Biochemistry & Molecular Biology 138 (2013) 132– 142.
- Karl-Heinz Storbeck, Liezl M. Bloem, Donita Africander, Lindie Schloms, Pieter Swart, Amanda C. Swart. 11 β -Hydroxydihydrotestosterone and 11-ketodihydrotestosterone, novel C19 steroids with androgenic activity: A putative role in castration resistant prostate cancer? Molecular and Cellular Endocrinology 377 (2013) 135–146.