The growth inhibitory effect of actein on human breast cancer cells is associated with activation of stress response pathways

Abstract

Previous studies indicate that the triterpene glycoside actein from the herb black cohosh inhibits growth of human breast cancer cells. This study seeks to identify genes altered in human breast cancer cells by treatment with actein, using gene expression analysis. We treated MDA-MB-453 human breast cancer cells with actein at 2 doses, 20 or 40 lg/mL, for 6 or 24 hr. We identified 5 genes that were activated after each of the treatments that are known to play a role in cellular responses to diverse stresses, including the DNA damage and unfolded protein responses. In addition, four genes that mediate the integrated stress response (ISR), including activating transcription factor 4, were induced under at least one of the 4 treatment conditions. We used hierarchical clustering to define clusters comprising patterns of gene expression. Two ISR genes, activating transcription factor 3 (ATF3) and DNA damage-inducible transcript 3, and lipid biosynthetic genes were activated after exposure to actein at 40 lg/ mL for 6 hr, whereas the cell cycle genes cyclin E2 and cell division cycle 25A were repressed. Our results suggest that actein induces 2 phases of the ISR, the survival phase and the apoptotic phase, depending on the dose and duration of treatment. We confirmed the results of gene expression analysis with real-time RT-PCR for 18 selected genes and Western blot analysis for ATF3. Since actein activated transcription factors that enhance apoptosis, and repressed cell cycle genes, it may be useful in the prevention and therapy of breast cancer. ' 2007 Wiley-Liss, Inc.

Nodal points and complexity of Notch-Ras signal integration

“…For a gene to be included in this study it must have passed set criteria for differential expression in at least 1 time point in comparisons between experimental and GAL4-only control embryos. Recent studies of gene expression using LIMMA have used the empirical Bayesian Log of Odds of differential expression factor (B) to identify differentially expressed genes (39,40). In our analysis we compared several different statistical approaches and found that using GC-RMA with LIMMA and thresholds of B Ͼ 0 and fold changes Ͼ1.5 to determine differential expression most enriched for known targets of Notch and Ras (data not shown).…”

Effects of black cohosh on estrogen biosynthesis in hippocampus of non-human primates ex vivo in vitro and in human neuroblastoma cells in vitro

“…Oral administration of iCR or E2 for 1 week to ovariectomized rats was able to restore neuronal excitability leading to functional recovery of hypothalamic activity [14,24]. Furthermore, iCR has been shown to upregulate genes related to cell survival under metabolic stress such as hypoxia [28][29][30]. In hypoestrogenic women, the cerebral blood flow has been shown to be reduced with regional patterns resembling those of patients with mild to moderate Alzheimer's disease [31].…”

Chemistry and pharmacology of saponins: special focus on cytotoxic properties

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