Breast Cancer Research – Prof Ann Louw
Prof Ann Louw
- Department of Biochemistry, University of Stellenbosch
Title of project
Cyclopia and breast cancer.
What is the aim of this project?
Cyclopia has been shown to have phytoestrogenic activity. Phytoestrogens have been proposed as an alternative to hormone replacement therapy (HRT) as epidemiological studies suggest that phytoestrogens may protect against hormone-induced cancers such as breast cancer, a possible adverse effect of HRT. Although the mechanism of protection is not well understood it has been suggested that the estrogen receptor beta (ERβ) selectivity of phytoestrogens may play a role in countering the proliferative action of ERalpha (ERα) in breast cancer. In addition, stimulation of sex hormone binding globulin (SHBG) transcription by phytoestrogens may be relevant as breast cancer risk has been shown to decrease with increased SHBG levels. Cyclopia extracts have been shown to act preferentially through ERβ, to interact with SHBG, and to attenuate estradiol-induced breast cancer cell proliferation and thus further investigation of the mechanism of action of Cyclopia phytoestrogens, and the possible role of SHBG, in modulating estrogen-dependent breast cancer is warranted.
Cyclopia, an indigenous South-African plant used to prepare honeybush tea, has phytoestrogenic activity and as such Cyclopia extracts have potential to be developed as a phytoestrogenic nutraceutical. One of the possible uses of such a nutraceutical would be for alleviation of menopausal symptoms. However, one of the concerns, as with traditional hormone replacement therapy (HRT), is that Cyclopia phytoestrogens may increase rather than decrease risk for breast cancer. The incidence of breast cancer is steadily rising and it is the commonest form of cancer amongst women in South Africa. Although breast cancer can affect women of all ages it occurs most commonly in women over the age of 50. Thus post-menopausal women are not only the group most at risk for breast cancer but also the group that would be interested in using HRT, whether traditional or in the form of phytoestrogen supplements.
Estrogen is one of the strongest inducers of breast cancer. Two receptors mediate the action of estrogen, ERalpha and ERbeta. It has been suggested that ERalpha is responsible for the proliferative action of estrogen in breast cancer while ERbeta attenuates the proliferative action mediated by ERalpha.
This study uses a basic research approach, with mainly biochemical and molecular biology techniques, to evaluate, in vitro and in vivo, the effects of Cyclopia phytoestrogenic extracts and select polyphenols on SHBG function, breast cancer proliferation and the modulation of breast cancer by SHBG.
Our recent results indicate that Cyclopia extracts do not transactivate genes via ERalpha but only via ERbeta. In addition, the Cyclopia extracts antagonise the transactivation of estradiol via ERalpha. This suggests that Cyclopia extracts could directly antagonise the proliferative action of estradiol on breast cancer cells. Furthermore, we show that Cyclopia extracts while reducing ERalpha levels, like estrogen, unlike estrogen, the extracts stabilise ERbeta. This suggests that the Cyclopia extracts may produce an ER milieu in breast cancer that is less conducive to proliferation. Although we find that when added alone Cyclopia extracts do induce proliferation of breast cancer cells, they do so at concentrations several orders of magnitude lower than estrogen suggesting that they are very weak inducers of proliferation. In addition, they antagonise the proliferative action of estrogen. Furthermore, the fact that Cyclopia extracts stimulate the production of SHBG, the protein binding estrogens in plasma, suggests that this could be an additional mechanism decreasing estrogens levels in circulation and limiting estrogen’s availability.
The current project will specifically focus on the mechanism of action of Cyclopia extracts in breast cancer and the modulating role that SHBG may play. This basic research evaluating the safety of Cyclopia extracts with regard to breast cancer could significantly enhance the scientific underpinning of any health claims made for Cyclopia extracts. Cyclopia extracts shown to be safe and efficacious could provide many women with a uniquely South African alternative to HRT. In addition, this investigation would contribute to the knowledge base concerning the effects of phytoestrogens in breast cancer, a topic that is still controversial.
These publications came out in 2008 and concern Cyclopia:
- C Mfenyana, E. Joubert, and A. Louw (2008) Selective extraction of Cyclopia for enhanced in vitro phytoestrogenicity and benchmarking against commercial phytoestrogen extracts. J Steroid Biochemistry and Molecular Biology 112, 74-86.
- E. Joubert, W.C.A. Gelderblom, A. Louw, and D. de Beer D. (2008) Chemical and biological perspectives of rooibos (Aspalathus linearis), honeybush (Cyclopia spp.) and bush tea (Athrixia phylicoides). Journal of Ethonopharmacology 119, 376–412. Click here to read the publication.
- Koch Visser, Morné Mortimer, Ann Louw. Cyclopia Extracts Act as ERα Antagonists and ERβ Agonists, In Vitro and In Vivo. Department of Biochemistry, University of Stellenbosch
- Koch Visser and Ann Louw. The molecular mechanism of action whereby phytoestrogenic extracts of Cyclopia modulates estrogen induction of breast cancer. Pposter presentation at SASBMB conference January 2012.
- Craig Andrews, Koch Visser, and Ann Louw. Cyclopia extracts and sex hormone binding globulin (SHBG). Poster presentation at SASBMB conference January 2012.
- Mornè F. Mortimer, Nicolette J. D. Verhoog, Ann Louw. Crosstalk between Estrogen and Glucocorticoid receptors: Investigating Cyclopia extracts. Poster presentation at SASBMB conference January 2012