Effects of a black cohosh extract on gene expression in MCF 7 cells were determined by means of Affymetrix GeneChip Human Genome U133 Plus selleckchem Paclitaxel 2. 0 arrays, ena bling almost complete Inhibitors,Modulators,Libraries analysis of the transcriptome. After treatment of MCF 7 cells for 24 h with the black cohosh extract at the IC50 concentration changes of the expression levels of 431 genes were detected using highly stringent selection criteria. Random permutation Inhibitors,Modulators,Libraries of gene expression profiles showed a mean of 22 to 32 regulated probe sets in our data set with our selection criteria indi cating a false positive rate of about 5%. Comparing the expression patterns, action of black cohosh is opposite to estradiol and more similar to tamoxifen regarding proliferation and cell survival.
How ever, the effect of black cohosh treatment appears more complex, as significantly more genes were regulated than either with E2 or tamoxifen. The genes regulated by black cohosh did not include Inhibitors,Modulators,Libraries well known estrogen regulated genes, with the exception of ESR1 and VEGF which both could be regulated via hypoxia response. In contrast, a wider range of cellular pathways and targets were affected by black cohosh but not E2 or tamoxifen. Hence, action of black cohosh in MCF 7 cells seems to be neither estrogenic nor antiestro genic but rather multifacetted. Because MCF 7 is a model for determining estrogenic or antiestrogenic effects, we can conclude that the benefical effects of black cohosh in alleviating postmenopausal complaints might be rather due to central nervous action via dopamine, serotonin or opioidic receptors.
Among all regulated genes, those related to the functional categories of proliferation and stress response were found to be highly significantly overrepresented, and these groups appear Inhibitors,Modulators,Libraries to be intercon nected. Given that many genes were regulated at a lower level and, therefore, excluded by the stringent filter set ting, a statistically highly significant accumulation of genes in these functional categories emphasizes the signif icance of our results. The cell cycle inhibition observed in the proliferation experiments appears to be due to an arrest at both G1 S and G2 M transition points, as indicated by an accumula tion of regulated genes. This finding is corroborated by recent results of Inhibitors,Modulators,Libraries a flow cytometric analysis. Several genes involved in apoptosis appeared to be regulated, most genes in a pro apoptotic manner.
Some genes are related to apoptotic as well as anti apoptotic events. These genes are linked to different cellular stress response mech anisms. Altogether, the expression levels of approxima tively 40 genes related to stress response Palbociclib were affected by black cohosh. Given the fact that results of stress response pathways are contradictory, pro and anti apoptotic gene expression may not be surprising. The main purpose of stress response is an adaptation of the cells to stress fac tors, resulting in cell survival, angiogenesis and promoted tumor growth.