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

• Published in: BMC cancer Vol. 16; no. 1; p. 707
• Main Authors: Cathcart, Mary-Clare, Useckaite, Zivile, Drakeford, Clive, Semik, Vikki, Lysaght, Joanne, Gately, Kathy, O'Byrne, Kenneth J, Pidgeon, Graham P
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 01.09.2016; BioMed Central
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Carcinoma, Non-Small-Cell Lung - pathology; Care and treatment; Cell Line, Tumor; Cell Proliferation - drug effects; Diagnosis; Flavanones - pharmacology; Gene expression; Gene Expression Profiling; Humans; Immunohistochemistry; Lung cancer, Non-small cell; Lung Neoplasms - pathology; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neovascularization; Polymerase Chain Reaction; Transcriptome - drug effects; Tumor Cells, Cultured; Xenograft Model Antitumor Assays; in-vivo; Baicalein; Angiogenesis; NSCLC; Survival; Apoptosis
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-016-2740-0

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.