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

Chun Ju Chang, Jen Hwey Chiu*, Ling Ming Tseng, Chuan Hsiung Chang, Tsu Ming Chien, Chien Chih Chen, Chew Wun Wu, Wing Yiu Lui

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish
Pages (from-to)967-976
Number of pages10
JournalMenopause
Volume13
Issue number6
DOIs
StatePublished - Nov 2006

Keywords

  • AKT
  • Breast cancer
  • ERK
  • HER-2
  • Menopause
  • Si-Wu-Tang

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