Anti-cancer effects of baicalein in non-small cell lung cancer in-vitro and in-vivo. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Cathcart, Mary-Clare; Useckaite, Zivile; Drakeford, Clive; Semik, Vikki; Lysaght, Joanne; Gately, Kathy; O'Byrne, Kenneth; Pidgeon, Graham
• Is Part Of: BMC cancer. Volume 16:Issue 1(2016)
• Page Start: 1
• Page End: 13
• Publication Date: 2016-12
• Subjects: Baicalein -- NSCLC -- Survival -- Apoptosis -- Angiogenesis -- in-vivo; Cancer -- Periodicals; 616.994005
• DOI: 10.1186/s12885-016-2740-0
• Languages: English
• ISSNs: 1471-2407

Abstract

Abstract Background Baicalein is a widely used Chinese herbal medicine derived fromScutellaria 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. Methods 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. Results 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 cellularf -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 bothVEGF andFGFR-2 following baicalein treatment, with a corresponding increase (p < 0.001) inRB-1 . Conclusion 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 ofVEGF, FGFR-2, andRB-1 have been implicated, suggesting a molecular mechanism underlying this in-vivo effect.