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Traditional Chinese Medicine in the Post-genomic era: identifying lead therapeutic compounds against cancer

Periodic Report Summary - TCMCANCER (Traditional Chinese Medicine in the Post-genomic era: identifying lead therapeutic compounds against cancer)

The objectives of this project were to:
(1) select a number of purified and chemically defined compounds from a library of more than 3000 purified compounds derived from herbal traditional Chinese medicine (TCM) extracts, many of which are known to show anticancer activities;
(2) identify a set of lead candidate compounds with anti-tumour activity by using high throughput screening technologies together with state of the art preclinical tumour models;
(3) determine their novelty as putative therapeutic compounds;
(4) determine their mechanism of action on the genomic level;
(5) determine their pharmacological parameters;
(6) determine their absorption mechanism and pharmacokinetic properties.

In the first two years, in an exchange volume of 37 person months involving five early-stage and eight experienced scientists, 275 selected purified compounds were tested (using cytotoxicity tests and live cell observations) in various cancer cell lines; also 12 compounds from three different plant species were purified and the structures of nine of them could be determined by nuclear magnetic resonance (NMR), but none of them were novel. Among the tested compounds, 22 were found to exhibit medium to high cytotoxic activities in at least one cancer cell line. TGFbeta1 inhibitory assays were established and used to screen 129 of the 275 compounds. Of all the active compounds identified, those that will be available in suitable amounts for in vivo assays will be used in the last two years of the project to test their anti-cancer and pharmacological properties in mouse models.