Anti-cancer effects of baicalein in non-small cell lung cancer in-vitro and in-vivo

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

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27 Citations (Scopus)

Abstract

Background: 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. 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 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. 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 of VEGF, FGFR-2, and RB-1 have been implicated, suggesting a molecular mechanism underlying this in-vivo effect.

Original languageEnglish
Article number707
JournalBMC Cancer
Volume16
Issue number1
DOIs
Publication statusPublished - 1 Sep 2016
Externally publishedYes

Keywords

  • Angiogenesis
  • Apoptosis
  • Baicalein
  • In-vivo
  • NSCLC
  • Survival

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    Cathcart, M. C., Useckaite, Z., Drakeford, C., Semik, V., Lysaght, J., Gately, K., O'Byrne, K. J., & Pidgeon, G. P. (2016). Anti-cancer effects of baicalein in non-small cell lung cancer in-vitro and in-vivo. BMC Cancer, 16(1), [707]. https://doi.org/10.1186/s12885-016-2740-0