Type

Journal Article

Authors

Graham P Pidgeon
Kenneth J O'Byrne
Kathy Gately
Joanne Lysaght
Vikki Semik
Clive Drakeford
Zivile Useckaite
Mary-Clare Cathcart

Subjects

Biochemistry

Topics
cancer anti cancer non small cell lung non small cell lung cancer nsclc cell cycle progression gene expression profiling cell proliferation scutellaria baicalenesis anti inflammatory small cell lung cancer

Anti-cancer effects of baicalein in non-small cell lung cancer in-vitro and in-vivo. (2016)

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.
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Full list of authors on original publication

Graham P Pidgeon, Kenneth J O'Byrne, Kathy Gately, Joanne Lysaght, Vikki Semik, Clive Drakeford, Zivile Useckaite, Mary-Clare Cathcart

Experts in our system

1
Graham Pidgeon
Trinity College Dublin
Total Publications: 38
 
2
Kenneth J O'Byrne
Trinity College Dublin
Total Publications: 37
 
3
Kathy Gately
Trinity College Dublin
Total Publications: 22
 
4
Joanne Lysaght
Trinity College Dublin
Total Publications: 39
 
5
Zivile Useckaite
Royal College of Surgeons in Ireland
Total Publications: 4
 
6
Mary Clare Cathcart
Trinity College Dublin
Total Publications: 16