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Estrogenic and antiproliferative activities of isoliquiritigenin in MCF7 breast cancer cells.

Licorice root contains chemically diverse compounds that exhibit estrogenic effects in vitro and in vivo. The chalcone isoliquiritigenin (ISL) is a component of licorice extract exhibiting either antitumorigenic activity or estrogen receptor (ER) alpha-dependent growth promoting effects on breast cancer cells. In order to contribute to a better understanding of this apparent paradox, we synthesized and ascertained the estrogenic properties of ISL using, as model systems, the hormone-sensitive MCF7 breast cancer cells and the steroid-independent HeLa cells.Transfection experiments reveal that ISL is able to transactivate the endogenous ER alpha in MCF7 cells and this is supported by the capability to induce down-regulation of ER alpha protein levels and up-regulation of pS2 mRNA. Moreover, by using chimeric proteins consisting of the hormone binding domains of ER alpha and ER beta fused to the Gal4 DNA binding domain, we have determined that ISL is an estrogenic agonist of both ER isoforms.As a biological counterpart, low and intermediate ISL concentrations that induce substantial transcriptional activity stimulate the proliferation of MCF7 cells. However, high levels of ISL become cytotoxic even in steroid-receptor negative HeLa cells. Thus, the activity of ISL and the balance between risk or chemopreventive factor for estrogen-dependent breast cancer may depend on dietary intake.[1]

References

  1. Estrogenic and antiproliferative activities of isoliquiritigenin in MCF7 breast cancer cells. Maggiolini, M., Statti, G., Vivacqua, A., Gabriele, S., Rago, V., Loizzo, M., Menichini, F., Amdò, S. J. Steroid Biochem. Mol. Biol. (2002) [Pubmed]
 
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