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Cancer Chemotherapy and Pharmacology

, Volume 68, Issue 5, pp 1315–1323 | Cite as

Furanodienone induces cell cycle arrest and apoptosis by suppressing EGFR/HER2 signaling in HER2-overexpressing human breast cancer cells

  • Ying-Wei Li
  • Guo-Yuan Zhu
  • Xiao-Ling Shen
  • Jian-Hong Chu
  • Zhi-Ling Yu
  • Wang-Fun FongEmail author
Original Article

Abstract

Purpose

Overexpression of EGFR and HER2 is seen in breast cancers and results in poor prognosis and decreased patient survival. Clinically, EGFR and HER2 are effective therapeutic targets. The objective of this study is to investigate the in vitro effects of furanodienone, an active chemical component isolated from Rhizoma Curcumae, on the activation of EGFR/HER2 signaling, cell cycle, and apoptosis in HER2-overexpressing BT474 and SKBR3 cells.

Methods

Cell growth was assessed by SRB protein assay. Cell cycle analysis was carried out by flow cytometry, and apoptosis was observed by Annexin V and DAPI staining. Effects of furanodienone on the activation of EGFR/HER2 signaling-related proteins were analyzed by western blotting.

Results

Furanodienone inhibited cell growth in BT474 and SKBR3 cells. Furanodienone caused G1 arrest in BT474 cells and induced apoptosis in SKBR3 cells. Furanodienone interfered with EGFR/HER2 signaling in treated cells as shown by decreases in phosphorylated EGFR, HER2, Akt, Gsk3β and an increase in p27kip1 protein. Accordingly, furanodienone inhibited EGF-induced phosphorylation of EGFR, HER2, Akt, and Gsk3β. EGFR-specific siRNA knockdown did not affect the cell growth inhibitory effect of furanodienone. On the contrary, specific siRNA knockdown of HER2 increased cellular resistance to furanodienone toxicity. In HER-2-deficient MDA-MB-231 cells, the transfection and expression of HER2 increased the sensitivity of cells to furanodienone toxicity.

Conclusion

Furanodienone inhibited EGFR/HER2 signaling pathway in BT474 and SKBR3 cells. More importantly, the effect of furanodienone was specifically dependent on HER2, but not EGFR, expression.

Keywords

Furanodienone EGFR HER2 Breast cancer 

Notes

Acknowledgments

We thank Dr. Richard K.W. Choy (Obstetrics and Gynaecology Department, The Chinese University of Hong Kong) for the generous gift of SKBR3 cell line. This work was supported by a Faculty Research Grant of Hong Kong Baptist University (FRG2/08-09/102).

Supplementary material

280_2011_1624_MOESM1_ESM.pdf (300 kb)
Supplementary material 1 (PDF 307 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Ying-Wei Li
    • 1
  • Guo-Yuan Zhu
    • 1
  • Xiao-Ling Shen
    • 1
  • Jian-Hong Chu
    • 1
  • Zhi-Ling Yu
    • 1
  • Wang-Fun Fong
    • 1
    Email author
  1. 1.School of Chinese Medicine, Center for Cancer and Inflammation ResearchHong Kong Baptist UniversityKowloon TongHong Kong, China

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