title: Gold nanoparticle-conjugated quercetin inhibits epithelial-mesenchymal transition, angiogenesis and invasiveness via EGFR/VEGFR-2-mediated pathway in breast cancer.
abstract: OBJECTIVE
  Epidermal growth factor plays a critical role in breast malignancies by enhancing cell proliferation, invasion, angiogenesis and metastasis. Epithelial-mesenchymal transition (EMT) is a crucial process by which epithelial cells lose polarity and acquire migratory mesenchymal properties. Gold nanoparticles are an efficient drug delivery vehicle for carrying chemotherapeutic agents to target cancer cells and quercetin is an anti-oxidative flavonoid known with potent anti-malignant cell activity.
  
  
  METHODS
  Cell viability was assessed by MTT assay, and protein expression was examined by Western blotting and immunocytochemistry. Cell invasion was monitored using invasion chambers, and cell migration was analysed by scratch wound-healing assay. In vitro and ex vivo angiogenesis studies were performed by capillary-like tube formation assay and chick embryo angiogenesis assay (CEA). 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary carcinoma in Sprague-Dawley rats.
  
  
  RESULTS
  We observed a significant reduction in protein expression of vimentin, N-cadherin, Snail, Slug, Twist, MMP-2, MMP-9, p-EGFR, VEGFR-2, p-PI3K, Akt and p-GSK3β, and enhanced E-cadherin protein expression in response to AuNPs-Qu-5 treatment. AuNPs-Qu-5 inhibited migration and invasion of MCF-7 and MDA-MB-231 cells compared to free quercetin. AuNPs-Qu-5-treated HUVECs had reduced cell viability and capillary-like tube formation. In vitro and in vivo angiogenesis assays showed that AuNPs-Qu-5 suppressed tube and new blood vessel formation. Treatment with AuNPs-Qu-5 impeded tumour growth in DMBA-induced mammary carcinoma in SD rats compared to treatment with free quercetin.
  
  
  CONCLUSIONS
  Our results suggest that AuNPs-Qu-5 inhibited EMT, angiogenesis and metastasis of the breast cancer cells tested by targeting the EGFR/VEGFR-2 signalling pathway.
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, India.
authors.forename: S
authors.initials: S
authors.lastname: Balakrishnan
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, India.
authors.forename: F A
authors.initials: FA
authors.lastname: Bhat
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, India.
authors.forename: P
authors.initials: P
authors.lastname: Raja Singh
authors.affiliation: Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, Telangana State, India.|Academy of Scientific and Innovative Research (AcSIR), Training and Development Complex, CSIR Campus, Taramani, Chennai, 600 113, India.
authors.forename: S
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, India.
authors.forename: P
authors.initials: P
authors.lastname: Elumalai
authors.affiliation: Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, Telangana State, India.|Academy of Scientific and Innovative Research (AcSIR), Training and Development Complex, CSIR Campus, Taramani, Chennai, 600 113, India.
authors.forename: S
authors.initials: S
authors.lastname: Das
authors.affiliation: Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, Telangana State, India.|Academy of Scientific and Innovative Research (AcSIR), Training and Development Complex, CSIR Campus, Taramani, Chennai, 600 113, India.
authors.forename: C R
authors.initials: CR
authors.lastname: Patra
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, India. j_arunakaran@hotmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Arunakaran
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001940:Breast / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006046:Gold / Q000494:pharmacology / Q000627:therapeutic use*; D061307:Human Umbilical Vein Endothelial Cells; D053758:Nanoparticles / Q000627:therapeutic use*; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011794:Quercetin / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D006046:Gold; D011794:Quercetin; D066246:ErbB Receptors; D040301:Vascular Endothelial Growth Factor Receptor-2