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Title: Investigation of some traditional Chinese medicines used to treat cancer
Author: Fang, Rui
Awarding Body: University of London
Current Institution: King's College London (University of London)
Date of Award: 2006
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The aim of the present project is to study five Traditional Chinese Medicines (TCM) used traditionally in China for the treatment of cancer. They are Dolichos lablab L., Gekko swinhonis Gunther, Illicium verum Hook. f, Lonicera japonica Thunb. and Iris tectorum Maxim. Solvent extractions of the TCMs were subjected to bioassay-guided fractionation and isolation, yielding series of fractions with increasing purity and cytotoxicity. The cytotoxicity assay used comprised four human cancer cell lines (COR-L23, C32, MCF-7 and HepG2) and two human normal cell lines (MRC-5 and 16HBE14o-). The separation of organic components was carried out mainly by means of TLC, VLC and HPLC. Isolation and purification of bioactive compounds from the active extract of I. tectorum, the most potent source tested, led to the identification of two known flavonoids (tectorigenin and 7-0-methyl-aromadendrin), two known triterpenes (isoiridogermanal and iridobelamal A) and two novel triterpenes. The structures of the latter were determined by mass spectrometry and infrared and 2D nuclear magnetic resonance spectroscopic techniques. Induction of apoptosis by the isolated compounds was investigated using flow cytometry with quadrant analysis, and confirmed by fluorescence microscopy. Furthermore, cell cycle specific cytotoxicity was determined by DNA analysis. The selectivity of cytotoxicity activity, modes of action and structure-activity relationships of the compounds are discussed. Also, a cell culture-based prodrug assay was established for high-throughput screening of potential glucosides, which are inactive in vitro but may be metabolized to active aglycones in vivo. In summary. the results obtained showed that selection based on ethnopharmacology, together with a robust and reliable method to detect biological activity, can be a useful approach for exploring traditional medicines for novel cytotoxic substances.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available