Chemopreventive and/or Chemotherapeutic Action of a Cyclopia Extract
Project ended 31 March 2018
Prof Ann Louw
Title of the project
Chemopreventive and/or chemotherapeutic action of a Cyclopia extract in rat models of breast cancer.
Globally and in South Africa breast cancer is the most frequent malignancy in women. Most breast cancers are oestrogen receptor (ER) positive and require oestrogen for growth and metastasis. Selective oestrogen receptor modulators (SERMs), such as tamoxifen, are used for both treatment and prevention of breast cancer, while oestrogen receptor down-regulators (SERDs), such fulvestrant, which are pure ER antagonists devoid of agonist effects, may be used in cases of tamoxifen resistance. The ideal SERM, with possible use in hormone replacement therapy and prevention of breast cancer, has been suggested to be anti-estrogenic in breast, neutral in the uterus and estrogenic in bone. Cyclopia or honeybush tea contains phytoestrogens. Previous work from our laboratory has suggested that an extract prepared from Cyclopia, SM6Met, has several properties that may make it an effective chemopreventative and/or chemotherapeutic agent for breast cancer. The current project aims to investigate the ability of SM6Met to prevent (chemopreventative) or treat (chemotherapeutic) breast cancer in two breast cancer models in rats. Furthermore, the effects of SM6Met in these models will be compared to that of tamoxifen and fulvestrant. In addition, an ER subtype specific ligand, liquiritigenin, will also be investigated as SM6Met has been shown to be an ER agonist.
The value of the project in the struggle against cancer:
Although current pharmacological chemoprevention options for breast cancer such as tamoxifen are effective, their high cost, low practicability and side-effect profile, make them unsuitable for chemoprevention aimed at the general population. Such public health interventions, which often include suitable dietary and lifestyle suggestions to the population, require low cost, high practicality and high tolerability. We have shown that honey bush extracts such as SM6Met can in rat models delay breast cancer tumour progression to the same extent as tamoxifen while displaying less side-effects. Thus honey bush tea displays the potential to be developed as a chemopreventative agent for breast cancer. However, for the implementation of rational chemoprevention strategies it is essential not only to assess safety and efficacy of candidate hemopreventative agents but also to understand their mechanisms of action, therefore more work is needed to understand the molecular mechanism of action of SM6Met. Furthermore, information regarding mechanism of action of honey bush may enhance the underpinnings of CANSA’s health campaigns, which aim to reduce cancer risk by identifying an edible consumer product, such as honey bush tea, which may assist in reducing cancer risk.
Future plans for the research project:
We submitted a new CANSA grant entitled “Molecular mechanisms of breast cancer risk reduction by SM6Met, a well characterized Cyclopia extract” where we want to further explore the chemopreventative mechanism of action of SM6Met. Although current pharmacological chemoprevention options are effective, their high cost, low practicability and sideeffect profile, make them unsuitable for chemoprevention aimed at the general population. Such public health interventions, which often include suitable dietary and lifestyle suggestions to the population, require low cost, high practicality and high tolerability. However, for the implementation of rational chemoprevention strategies it is essential not only to assess safety and efficacy of candidate chemopreventative agents but also to understand their mechanisms of action.