Cyclopia extracts act as ERα antagonists and ERβ agonists, in vitro and in vivo
Date
2013-11
Authors
Visser, Koch
Mortimer, Morne
Louw, Ann
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science (PLOS)
Abstract
Hormone replacement therapy associated risks, and the concomitant reluctance of usage, has instigated the search
for new generations of estrogen analogues that would maintain estrogen benefits without associated risks.
Furthermore, if these analogues display chemo-preventative properties in breast and endometrial tissues it would be
of great value. Both the selective estrogen receptor modulators as well as the selective estrogen receptor subtype
modulators have been proposed as estrogen analogues with improved risk profiles. Phytoestrogen containing
extracts of Cyclopia, an indigenous South African fynbos plant used to prepare Honeybush tea may serve as a
source of new estrogen analogues. In this study three extracts, P104, SM6Met, and cup-of-tea, from two species of
Cyclopia, C. genistoides and C. subternata, were evaluated for ER subtype specific agonism and antagonism both in
transactivation and transrepression. For transactivation, the Cyclopia extracts displayed ERα antagonism and ERβ
agonism when ER subtypes were expressed separately, however, when co-expressed only agonism was uniformly
observed. In contrast, for transrepression, this uniform behavior was lost, with some extracts (P104) displaying
uniform agonism, while others (SM6Met) displayed antagonism when subtypes were expressed separately and
agonism when co-expressed. In addition, breast cancer cell proliferation assays indicate that extracts antagonize cell
proliferation in the presence of estrogen at lower concentrations than that required for proliferation. Furthermore, lack
of uterine growth and delayed vaginal opening in an immature rat uterotrophic model validates the ERα antagonism
of extracts observed in vitro and supports the potential of the Cyclopia extracts as a source of estrogen analogues
with a reduced risk profile.
Description
The original publication is available at http:/www.plosone.org
Publication of this article was funded by the Stellenbosch University Open Access Fund.
Publication of this article was funded by the Stellenbosch University Open Access Fund.
Keywords
Estrogen -- Receptors, Estrogen -- Antagonists, Hormone replacement therapy
Citation
Visser, K., Mortimer, M. & Louw, A. 2013. Cyclopia Extracts Act as ERα Antagonists and ERβ Agonists, In Vitro and In Vivo. PLoS ONE 8(11), e79223, doi:10.1371/journal.pone.0079223