Si-Wu-Tang and its constituents promote mammary duct cell proliferation by up-regulation of HER-2 signaling

Menopause. 2006 Nov-Dec;13(6):967-76. doi: 10.1097/01.gme.0000227025.96686.8b.

Abstract

Objective: The consumption of over-the-counter natural products by perimenopausal women remains a challenging problem. It is our aim to investigate the proliferative effect of Si-Wu-Tang (SWT) and its constituents on MCF7 breast cancer cells as well as the SWT-modulated cell signaling and HER-2 gene expression.

Design: By using the MCF7 (ER+, HER-2 low), BT474 (ER+, HER-2 high), MDAMB231 (ER-, HER-2 low), and SKBR3 (ER-, HER-2 high) mammary duct cell lines as our in vitro model, the mitogenic effects of SWT and its constituents were assessed by trypan blue dye exclusion assay and DNA flow cytometry. SWT-modulated cell signaling and HER-2 gene expression were evaluated in the MCF7 line by Western blot and reverse transcriptase-polymerase chain reaction analyses.

Results: The results showed that SWT and some of its constituents dose-dependently stimulated cell proliferation of MCF7 cells. The activation of HER-2, its downstream signaling molecules AKT and ERK1/2, as well as HER-2 gene up-regulation were involved in SWT-stimulated cell proliferation. The addition of neutralizing antibody against HER-2 abrogated the SWT-up-regulated HER-2 expression, indicating a positive feedback control for the action of HER-2 in this setting. Ferulic acid, one of the major compounds in SWT, not only promoted cell proliferation of MCF7, BT474, MDAMB231, and SKBR3 cells, but also increased the phosphorylation of HER-2, AKT, and ERK1/2, as well as overexpression of HER-2, on MCF7 cells.

Conclusions: We conclude that SWT and its active constituents stimulate mammary duct cell proliferation by modulating HER-2, PI3K/AKT, and MAPK signaling and the positive feedback of HER-2 gene expression. This provides important information for perimenopausal women who are at risk of or have breast cancer or other growths in breast tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / pharmacology*
  • Estrogen Receptor alpha / drug effects
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, erbB-2 / drug effects*
  • Humans
  • Mammary Glands, Human / cytology
  • Mammary Glands, Human / drug effects*
  • Mitogen-Activated Protein Kinases / drug effects
  • Phosphorylation / drug effects
  • Plant Extracts / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Up-Regulation

Substances

  • Drugs, Chinese Herbal
  • Estrogen Receptor alpha
  • Plant Extracts
  • si-wu-tang
  • Mitogen-Activated Protein Kinases