Department of Biochemistry, Stellenbosch University, Stellenbosch 7600, South Africa; Department of Food Science, Stellenbosch University, Stellenbosch 7600, South Africa; Post-Harvest and Wine Technology Division, ARC Infruitec-Nietvoorbij, Stellenbosch 7600, South Africa
Verhoog, N.J.D., Department of Biochemistry, Stellenbosch University, Stellenbosch 7600, South Africa; Joubert, E., Department of Food Science, Stellenbosch University, Stellenbosch 7600, South Africa, Post-Harvest and Wine Technology Division, ARC Infruitec-Nietvoorbij, Stellenbosch 7600, South Africa; Louw, A., Department of Biochemistry, Stellenbosch University, Stellenbosch 7600, South Africa
Unfermented C. genistoides methanol extracts of different harvestings and selected polyphenols were evaluated for phytoestrogenic activity by comparing binding to both ER subtypes, transactivation of an ERE-containing promoter reporter, proliferation of MCF-7-BUS and MDA-MB-231 breast cancer cells, and binding to SHBG. The extracts from one harvesting of C. genistoides (P104) bound to both ER subtypes. All extracts transactivated ERE-containing promoter reporters via ERβ but not via ERα. All extracts, except P122, caused proliferation of the estrogen-sensitive MCF-7-BUS cells. Proliferation of MCF-7-BUS cells was ER-dependent as ICI 182,780 reversed proliferation. Physiologically more relevant, extracts antagonized E2-induced MCF-7-BUS cell proliferation. Furthermore, all extracts, except P122, induced proliferation of the estrogen-insensitive MDA-MB-231 cells, suggesting that the extracts are able to induce ER-dependent and ER-independent cell proliferation. Binding to SHBG by extracts was also demonstrated. These results clearly show that C. genistoides methanol extracts display phytoestrogenic activity and act predominantly via ERβ. HPLC and LC-MS analysis, however, suggests that the observed phytoestrogenic activity cannot be ascribed to polyphenols known to be present in other Cyclopia species. © 2007 American Chemical Society.
estrogen receptor alpha; estrogen receptor beta; flavonoid; phenol derivative; phytoestrogen; plant extract; polyphenols; unclassified drug; animal; article; cell strain COS1; Cercopithecus; chemistry; legume; physiology; Animals; Cercopithecus aethiops; COS Cells; Estrogen Receptor alpha; Estrogen Receptor beta; Fabaceae; Flavonoids; Phenols; Phytoestrogens; Plant Extracts; Cyclopia genistoides