HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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 microg/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 microg/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.
AuthorsLinda Saxe Einbond, Tao Su, Hsan-Au Wu, Richard Friedman, Xiaomei Wang, Alejandro Ramirez, Fredi Kronenberg, I Bernard Weinstein
JournalInternational journal of cancer (Int J Cancer) Vol. 121 Issue 9 Pg. 2073-2083 (Nov 01 2007) ISSN: 0020-7136 [Print] United States
PMID17621630 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright (c) 2007 Wiley-Liss, Inc.
Chemical References
  • ATF3 protein, human
  • Activating Transcription Factor 3
  • RNA, Messenger
  • Saponins
  • Triterpenes
  • actein
Topics
  • Activating Transcription Factor 3 (genetics, metabolism)
  • Animals
  • Breast Neoplasms (genetics, metabolism, pathology)
  • Cell Cycle (drug effects)
  • Cell Line
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Molecular Structure
  • Multigene Family (genetics)
  • Polymerase Chain Reaction
  • RNA, Messenger (genetics)
  • Saponins (chemistry, pharmacology)
  • Time Factors
  • Triterpenes (chemistry, pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: