title: Furanodienone induces cell cycle arrest and apoptosis by suppressing EGFR/HER2 signaling in HER2-overexpressing human breast cancer cells.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: School of Chinese Medicine, Center for Cancer and Inflammation Research, Hong Kong Baptist University, 4/F, JCSCM Building, 7 Baptist University Road, Kowloon Tong, Hong Kong, China.
authors: Ying-Wei
authors: YW
authors: Li
authors: Guo-Yuan
authors: GY
authors: Zhu
authors: Xiao-Ling
authors: XL
authors: Shen
authors: Jian-Hong
authors: JH
authors: Chu
authors: Zhi-Ling
authors: ZL
authors: Yu
authors: Wang-Fun
authors: WF
authors: Fong
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D012717:Sesquiterpenes; C559478:furanodienone