Cancer: Breast
Action: Inhibits metastasis, inhibits angiogenesis
Glabridin is a novel phytoestrogen isolated from licorice extract (Glycyrrhiza glabra (L.))
Breast Cancer Growth; Estrogen agonist
Glabridin and its derivatives bind to the human ER and have been found to act as an estrogen agonist in the induction of an estrogen response marker, such as CK activity, in vivo, to induce uterus wet weight, and to stimulate human breast cancer cell growth. There is an increasing demand for natural compounds that improve women's health by mimicking the critical benefits of estrogen to the bones and the cardiovascular system but avoiding its deleterious effects on the breast and uterus.
The estrogenic properties of glabridin, the major isoflavan in licorice root, were tested in view of the resemblance of its structure and lipophilicity to those of estradiol. The results indicate that glabridin is a phytoestrogen, binding to the human estrogen receptor and stimulating creatine kinase activity in rat uterus, epiphyseal cartilage, diaphyseal bone, aorta, and left ventricle of the heart. This indicates that isoflavans have estrogen-like activities. Glabridin and its derivatives exhibited varying degrees of estrogen receptor agonism in different tests and demonstrated growth-inhibitory actions on breast cancer cells (Tamir et al., 2000).
Inhibits Metastasis, Inhibits Angiogenesis
Glabridin exhibited effective inhibition of cell metastasis by decreasing cancer cell migration and invasion of metastatic MDA-MB-231 breast cancer cells. In addition, glabridin also blocked human umbilical vein endothelial cells (HUVEC) migration and decreased MDA-MB-231-mediated angiogenesis. Further investigation revealed that the inhibition of cancer angiogenesis by glabridin was also evident in a nude mice model. Blockade of MDA-MB-231 cells and HUVEC migration was associated with an increase of αγβ3 integrin proteosome degradation. Glabridin also decreased the active forms of FAK and Src, and enhanced levels of inactivated phosphorylated Src (Tyr 416), decreasing the interaction of FAK and Src.
Inhibition of the FAK/Src complex by glabridin also blocked AKT and ERK1/2 activation, resulting in reduced activation of RhoA as well as myosin light chain phosphorylation. This study demonstrates that glabridin may be a novel anti-cancer agent for the treatment of breast cancer in three different ways: inhibition of migration, invasion and angiogenesis (Hsu et al., 2011).
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