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, Zhiling YU, David W F FONG*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

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 p27 kip1 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.

Original languageEnglish
Pages (from-to)1315-1323
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume68
Issue number5
DOIs
Publication statusPublished - Nov 2011

Scopus Subject Areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

User-Defined Keywords

  • Breast cancer
  • EGFR
  • Furanodienone
  • HER2

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