Activation of rapid signaling pathways and the subsequent transcriptional regulation for the proliferation of breast cancer MCF-7 cells by the treatment with an extract of Glycyrrhiza glabra root

Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17 beta-estradiol (E-2), although glycyrrhizin did not show such an activity. Moreover, the estrogen receptor alpha-dependent neurite outgrowth induced by the extract was similar to that by E2, whereas glycyrrhizin had no effect. Furthermore, the expression profile examined by cDNA microarray assay using a set of 120 estrogen-responsive genes, which were related to proliferation, transcription, transport, enzymes and signaling, showed a statistically significant correlation (R = 0.47, P < 0.0001) between the profiles for E-2 and the extract. However, the expression profile for glycyrrhizin was different from that of the extract and E-2. The results indicate that rapid signaling pathways, including Erk1/2 and Akt, and the subsequent transcriptional regulation are involved in the proliferation of MCF-7 cells induced by the extract of G. glabra root. Furthermore, the extract had estrogenic activity and a distinguishable profile of gene expression, suggesting the presence of potentially useful components other than glycyrrhizin in G. glabra root for hormone and anti-cancer therapies. (c) 2007 Elsevier Ltd. All rights reserved.