HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells.

Abstract
Although tamoxifen (TAM) is used for the front-line treatment and prevention of estrogen receptor-positive (ER+) breast tumors, nearly 40% of estrogen-dependent breast tumors do not respond to TAM treatment. Moreover, the positive response is usually of short duration, and most tumors eventually develop TAM-resistance. Overexpression of HER2 gene is associated with TAM-resistance of breast tumor, and suppression of HER2 expression enhances the TAM activity. Soy isoflavone genistein has been shown to have anti-cancer activities and suppress expression of HER2 and ERalpha. The objective of this study was to test the hypothesis that genistein may sensitize the response of ER+ and HER2-overexpressing breast cancer cells to TAM treatment. The combination treatment of TAM and genistein inhibited the growth of ER+/HER2-overexpressing BT-474 human breast cancer cells in a synergistic manner in vitro. Determination of cellular markers indicated that this synergistic inhibitory effect might be contributed in part from combined effects on cell-cycle arrest at G(1) phase and on induction of apoptosis. Further determination of the molecular markers showed that TAM and genistein combination synergistically induced BT-474 cell apoptosis in part by synergistic downregulation of the expression of survivin, one of the apoptotic effectors, and downregulation of EGFR, HER2, and ERalpha expression. Our research may provide a novel approach for the prevention and/or treatment of TAM insensitive/resistant human breast cancer, and warrants further in vivo studies to verify the efficacy of genistein and TAM combination on the growth of ER+/HER2-overexpressing breast tumors and to elucidate the in vivo mechanisms of synergistic actions.
AuthorsZhiming Mai, George L Blackburn, Jin-Rong Zhou
JournalMolecular carcinogenesis (Mol Carcinog) Vol. 46 Issue 7 Pg. 534-42 (Jul 2007) ISSN: 0899-1987 [Print] United States
PMID17295235 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright(c) 2007 Wiley-Liss, Inc.
Chemical References
  • Receptors, Estrogen
  • Tamoxifen
  • Genistein
  • Receptor, ErbB-2
  • Caspases
Topics
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Apoptosis (drug effects)
  • Breast Neoplasms (drug therapy, metabolism, pathology)
  • Caspases (metabolism)
  • Cell Line, Tumor (drug effects)
  • Cell Proliferation
  • Drug Synergism
  • Genistein (administration & dosage)
  • Humans
  • Neoplasms, Hormone-Dependent (drug therapy, metabolism, pathology)
  • Receptor, ErbB-2 (metabolism)
  • Receptors, Estrogen (metabolism)
  • Tamoxifen (administration & dosage)

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: