title: Phytoestrogens induce apoptosis via extrinsic pathway, inhibiting nuclear factor-kappaB signaling in HER2-overexpressing breast cancer cells.
abstract: BACKGROUND
  Phytoestrogens are known to prevent tumor induction. But their molecular mechanisms of action are largely unknown. This study aimed to examine the effect of genistein and quercetin on proliferation and apoptosis in HER2-expressing breast cancer cells.
  
  
  METHODS
  The antiproliferative effects of phytoestrogens were tested by proliferation assays. Flow cytometry was performed to analyze the cell cycle. The effect of phytoestrogens on cell-signaling molecules was determined by Western blotting.
  
  
  RESULTS
  Genistein and quercetin inhibited the proliferation of MCF-7 vec and MCF-7 HER2 cells. This growth inhibition was accompanied with an increase of subG(0)/G(1) apoptotic fractions. Genistein and quercetin induced extrinsic apoptosis pathway, up-regulating p53. Genistein and quercetin reduced the phosphorylation level of IκBα, and abrogated the nuclear translocation of p65 and its phosphorylation within the nucleus.
  
  
  CONCLUSIONS
  Genistein and quercetin exert their antiproliferative activity by inhibiting NFκB signaling. Phytoestrogens could be potential useful compounds to prevent or treat HER2-overexpressing breast cancer.
authors.affiliation: Laboratory of Clinical Biology and Pharmacogenomics and Center for Clinical Research and Genomics, Institute of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Seo
authors.forename: Han Seok
authors.initials: HS
authors.lastname: Choi
authors.forename: Hyeong Sim
authors.initials: HS
authors.lastname: Choi
authors.forename: Youn Kyung
authors.initials: YK
authors.lastname: Choi
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Um
authors.forename: Inhwa
authors.initials: I
authors.lastname: Choi
authors.forename: Yong Cheol
authors.initials: YC
authors.lastname: Shin
authors.forename: Seong-Gyu
authors.initials: SG
authors.lastname: Ko
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D048789:Phytoestrogens / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D019941:Cyclin-Dependent Kinase Inhibitor p16; D048049:Extracellular Signal-Regulated MAP Kinases; D019833:Genistein; D048031:JNK Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D048789:Phytoestrogens; D051057:Proto-Oncogene Proteins c-akt; D011794:Quercetin; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; D048051:p38 Mitogen-Activated Protein Kinases; C115163:CREB1 protein, human; C508053:ERBB2 protein, human