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Li, Xinyu (2018) Anti-breast cancer activity of Coptidis Rhizoma-Euodiae Fructus formulae. Doctoral thesis, London Metropolitan University.
Coptidis rhizoma and Euodiae fructus have been used as herbal medicine in Asian countries including China for more than two thousand years. The bioactivities of the crude extracts and isolated compounds of both herbs have been widely reported including anti-cancer activity. Dual herbal formulae combined with Coptis and Euodia with different ratio have been clinically used to treat multiple digestive system disorders. The aims of this research are to evaluate the anti-breast cancer potential of Coptis-Euodia formulae, and standard alkaloids berberine and evodiamine, associated with their possible mechanisms as anti-cancer agent candidates. Thereby, a hypothesis of “Interaction and synergy between compounds might enhance, reduce, or even revise the bioactivities of medicinal herbs and their formulae compared with bioactive components isolated from them.” is to be proved.
MTT colorimetric assay, scratch wound-healing assay along with adhesion assay have been used to evaluate anti-breast cancer activities of Coptis-Euodia formulae and standard alkaloids. Cell cycle analysis along with topoisomerase I relaxation assay and topoisomerase II decatanation assay were operated to understand the anti-cancer mechanisms of them.
Anti-proliferative activity of Zuo Jin pill (Coptis : Euodia = 6 : 1) against both MDA-MB-231 and MCF-7 human breast cancer cell lines has been proved to be the strongest of the three dual herb combination with IC50 values of 0.16 and 0.19 mg/mL. Coptis-Euodia inhibited the cellular migration and adhesion ability of MDA-MB-231 cells which suggested the anti-metastasis potential. Results indicated that Coptis dominated the anti-cancer activities of Coptis-Euodia formulae with the contribution of berberine. Cell cycle analysis describes one of the anti-cancer mechanisms of Coptis-Euodia extracts. Berberine (5 μM) arrested over 60% of MDA-MB-231 cells at G0/G1 phase with 24 hrs treatment, while evodiamine (10 μM) arrested over 90% of MDA-MB-231 and 70% of MCF-7 cells at G2/M phase after 24 hrs. However, the cell cycle arresting activity of evodiamine did not reflect on the Euodia included herbal extracts. TCM formulae, with the presence of Coptis, arrested MDA-MB-231 cells at G0/G1 phase to a great extent. The effects of Coptis-Euodia extracts on DAN topoisomerase I and II further explained the possible anti-breast cancer mechanism of these herbal medicine formulae. All Coptis-Euodia extracts exhibited topoisomerase poison like activities in a concentration-dependent manner. Berberine has been confirmed to behave as a DNA intercalator at 100 μM while evodiamine did not show topoisomerase inhibition activity at the same concentration. Chapter six attempted to establish fluorescence based assay targeted sodium and calcium ion channels on cell membrane.
This study is concluded with a discussion of combination therapy potential of herbal medicine and a novel conception of “Artificial Herbal Medicine” which is expected to improve the understanding of traditional used herbal formulae and the standardization of herbal medicine.
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