Reference Profile Correlation Reveals Estrogen-like Trancriptional Activity of Curcumin

Background: Several secondary metabolites from herbal nutrient products act as weak estrogens (phytoestrogens), competing with endogenous estrogen for binding to the estrogen receptors and inhibiting steroid converting enzymes. However, it is still unclear whether these compounds elicit estrogen dependent transcription of genes at physiological concentrations. Methods: We compare the effects of physiological concentrations (100 nM) of the two phytoestrogens Enterolactone and Quercetin and the suspected phytoestrogen Curcumin on gene expression in the breast cancer cell line MCF7 with the effects elicited by 17-beta-estradiol (E2). Results: All three phytocompounds have weak effects on gene transcription; most of the E2 genes respond to the phytoestrogens in the same direction though to a much lesser extent and in the order Curcumin > Quercetin > Enterolactone. Gene regulation induced by these compounds was low for genes strongly induced by E2 and similar to the latter for genes only weakly regulated by the classic estrogen. Of interest with regard to the treatment of menopausal symptoms, the survival factor Birc5/survivin and the oncogene MYBL1 are strongly induced by E2 but only marginally by phytoestrogens. Conclusion: This approach demonstrates estrogenic effects of putative phytoestrogens at physiological concentrations and shows, for the first time, estrogenic effects of Curcumin. Copyright (C) 2010 S. Karger AG, Base

The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice

Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel