title: Anti-cancer effects of baicalein in non-small cell lung cancer in-vitro and in-vivo.
abstract: Baicalein is a widely used Chinese herbal medicine derived from Scutellaria baicalenesis, which has been traditionally used as anti-inflammatory and anti-cancer therapy. In this study we examined the anti-tumour pathways activated following baicalein treatment in non-small cell lung cancer (NSCLC), both in-vitro and in-vivo.
  
  
  
  The effect of baicalein treatment on H-460 cells in-vitro was assessed using both BrdU assay (cell proliferation) and High Content Screening (multi-parameter apoptosis assay). A xenograft nude mouse model was subsequently established using these cells and the effect of baicalein on tumour growth and survival assessed in-vivo. Tumours were harvested from these mice and histological tissue analysis carried out. VEGF, 12-lipoxygenase and microvessel density (CD-31) were assessed by immunohistochemistry (IHC), while H and E staining was carried out to assess mitotic index. Gene expression profiling was carried out on corresponding RNA samples using Human Cancer Pathway Finder Arrays and qRT-PCR, with further gene expression analysis carried out using qRT-PCR.
  
  
  
  Baicalein significantly decreased lung cancer proliferation in H-460 cells in a dose dependent manner. At the functional level, a dose-dependent induction in apoptosis associated with decreased cellular f-actin content, an increase in nuclear condensation and an increase in mitochondrial mass potential was observed. Orthotopic treatment of experimental H-460 tumours in athymic nude mice with baicalein significantly (p < 0.05) reduced tumour growth and prolonged survival. Histological analysis of resulting tumour xenografts demonstrated reduced expression of both 12-lipoxygenase and VEGF proteins in baicalein-treated tumours, relative to untreated. A significant (p < 0.01) reduction in both mitotic index and micro-vessel density was observed following baicalein treatment. Gene expression profiling revealed a reduction (p < 0.01) in both VEGF and FGFR-2 following baicalein treatment, with a corresponding increase (p < 0.001) in RB-1.
  
  
  
  This study is the first to demonstrate efficacy of baicalein both in-vitro and in-vivo in NSCLC. These effects may be mediated in part through a reduction in both cell cycle progression and angiogenesis. At the molecular level, alterations in expression of VEGF, FGFR-2, and RB-1 have been implicated, suggesting a molecular mechanism underlying this in-vivo effect.
authors: Department of Surgery, Trinity Translational Medicine Insitiute, Trinity Health Sciences Centre, Trinity College Dublin/St. James' Hospital, Dublin 8, Ireland.
authors: Mary-Clare
authors: MC
authors: Cathcart
authors: Department of Surgery, Trinity Translational Medicine Insitiute, Trinity Health Sciences Centre, Trinity College Dublin/St. James' Hospital, Dublin 8, Ireland.
authors: Zivile
authors: Z
authors: Useckaite
authors: Department of Surgery, Trinity Translational Medicine Insitiute, Trinity Health Sciences Centre, Trinity College Dublin/St. James' Hospital, Dublin 8, Ireland.
authors: Clive
authors: C
authors: Drakeford
authors: Department of Surgery, Trinity Translational Medicine Insitiute, Trinity Health Sciences Centre, Trinity College Dublin/St. James' Hospital, Dublin 8, Ireland.
authors: Vikki
authors: V
authors: Semik
authors: Department of Surgery, Trinity Translational Medicine Insitiute, Trinity Health Sciences Centre, Trinity College Dublin/St. James' Hospital, Dublin 8, Ireland.
authors: Joanne
authors: J
authors: Lysaght
authors: Department of Clinical Medicine, Institute of Molecular Medicine, Trinity Health Centre, Trinity College Dublin/St. James' Hospital, Dublin 8, Ireland.
authors: Kathy
authors: K
authors: Gately
authors: Cancer and Aging Research Program, Queensland University of Technology, Brisbane, Queensland, Australia.
authors: Kenneth J
authors: KJ
authors: O'Byrne
authors: Department of Surgery, Trinity Translational Medicine Insitiute, Trinity Health Sciences Centre, Trinity College Dublin/St. James' Hospital, Dublin 8, Ireland. pidgeong@tcd.ie.
authors: Graham P
authors: GP
authors: Pidgeon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016133:Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D044950:Flavanones; C006680:baicalein
keywords: Angiogenesis; Apoptosis; Baicalein; NSCLC; Survival; in-vivo