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Anti-cancer effects of baicalein in non-small cell lung cancer in-vitro and in-vivo
Pidgeon, Graham; Lysaght, Joanne; O'Byrne, Ken; Gately, Kathy
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
Keyword(s): Scutellaria baicalenesis; Cancer
Publication Date:
2016
Type: Journal article
Peer-Reviewed: Yes
Language(s): English
Institution: Trinity College Dublin
Citation(s): Cathcart M.-C, Useckaite Z, Drakeford C, Semik V, Lysaght J, Gately K, O'Byrne K.J, Pidgeon G.P, Anti-cancer effects of baicalein in non-small cell lung cancer in-vitro and in-vivo, BMC Cancer, 16, 1, 2016, 707-
First Indexed: 2017-07-05 05:36:13 Last Updated: 2019-11-29 07:15:48