Investigation of the anti-tumour effects of Scutellaria barbata and Scutellaria baicalensis on human lung cell lines

PhD Thesis


Gao, Jiayu 2010. Investigation of the anti-tumour effects of Scutellaria barbata and Scutellaria baicalensis on human lung cell lines. PhD Thesis University of East London School of Health, Sport and Bioscience
AuthorsGao, Jiayu
TypePhD Thesis
Abstract

Despite improvements in lung cancer therapy over recent years, the 5-year survival rate has not dramatically changed and the development of more effective cancer therapy remains an ongoing challenge. Scutellaria baicalensis (S. baicalensis) and Scutellaria barbata (S. barbatd) are widely used in Chinese medicine as a traditional adjuvant to chemotherapy of lung cancer. However, their functional biomarkers and underlying mechanisms remain unclear.
In this study, cytotoxic assays (MTT, LDH and Trypan-Blue) demonstrated that the ethanol extracts of both S. baicalensis and S. barbata had selective growth inhibitory
effects on lung cancer A549, SK-LU-1 and SK-MES-1 cells, but not normal lung fibroblasts. These activities were then mapped onto the secondary metabolite profile of S. baicalensis and S. barbata by principal components analysis (PCA) of proton NMR and HPLC-UV data. Flavonoid compounds, baicalin, baicalein and wogonin, were then determined as the functional biomarkers that contribute to the cytotoxic
activity of S. baicalensis on human lung cancer cells. Two compounds (p66 and p72,to be identified) were determined as functional biomarkers of S. barbata.
Furthermore, propidium iodide-mediated analysis revealed that the cell cycle was arrested at Go/Gi phase on SK-LU-1 and SK-MES-1 cells, while it was arrested at S phase on A549 cells under Scutellaria treatment. The treatment also led to apoptosis of A549, SK-LU-1 and SK-MES-1 cells in the Annexin-V assay. In order to elucidate molecular mechanisms, fluorescence 2-D Difference Gel Electrophophoresis was used and proteins differentially expressed (DE) during S. baicalensis treatment were identified by MALDI-TOF MS/Protein Fingerprint. Fifteen DE proteins altered most(increased or decreased more than 5-fold) were identified and found to be related to cellular processes including inhibiting self-sufficiency of growth signals (human enoclase 1, annexin I, ALDH1A1, peroxiredoxin 1, and nucleophosmin), inducing apoptosis (prohibitin, annexin I, protein disulfide isomerase, peroxiredoxin 1, HSP70, HSP27 and UCHL1) and increasing sensitivity to anti-growth signals (triosephosphate
isomerase 1, ALDH1A1, peroxiredoxin 1, DJ-1, and MN-superoxide dismutase).
Moreover, specific immunoblotting identification showed an increased expression of p53 and BAX, which initiated and enhanced the apoptosis in cancer cells. The
expression of Cyclin A decreased while cyclin Dl remained constant and contributed to the S phase arrest of A549. In treated SK-MES-1 cells, the expression of cyclin Dl
decreased while cyclin A remained constant and led to Go/Gi phase arrest.
Overall, these results encourage further investigations on the molecular mechanisms to support existing clinical use of S. baicalensis and S. barbata as an adjuvant to lung
cancer therapy.

KeywordsLung cancer; Chemotherapy; Chinese medicine
Year2010
Publication dates
PrintMay 2010
Publication process dates
Deposited12 Sep 2013
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