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Title

Molecular mechanisms study of effective constituents in Coptidis Rhizoma on cancer-specific metabolic reprogramming

English Abstract

Berberine is an isoquinoline alkaloid with diversified pharmacological activities, mainly derived from Chinese material medica Coptidis Rhizoma (Huang Lian) and widely used as a gastrointestinal remedy in China. In modern pharmacology, the anti-tumor activity of berberine obtained a wealth of research results and strongly tied to the characteristics of dissipating heat and detoxifying from Chinese medicine principles. Meanwhile, the effect with communal characteristics on hypoglycemic, hypolipidemic and hypercholesterolemia, also on diabetes and obesity in clinic implied metabolic regulation potential of berberine. The combination of anti-tumor effect and metabolic regulation would give birth to cancer metabolism reprogramming. It was characterized by metabolic regulation dysfunction and existed as a state of homeostasis imbalance. Cancer metabolism reprogramming is a complex system with numerous biochemical pathways adequately responding to fast-changing metabolic state. And Chinese medicine principles also have an adaptation-eternal theme of biological evolution, emphasizing on holistic health and syndromes differentiation in a whole organism system. Therefore, energy homeostasis of cancer cells is similar to Chinese medicine principles, both are dynamic systems with regulatory networks. This relationship also supported hypothesis of anti-tumor effect of berberine through a metabolic control. Hence, we investigated anti-tumor effect from metabolic perspective and attempted to find the potential targets in berberine’s effect on cancer cells metabolism from interdisciplinary view, in order to imply the communal pathways in cancer, diabetes and obesity and provide an in-depth perspective and various perspectives in mechanism research. Human breast cancer cell lines MCF-7 and MDA-MB-231 iv were applied to investigate anti-tumor effect of Coptidis Rhizoma constitutes, and the effective constitute berberine was focused on the three aspects of cancer cells metabolism simultaneously. Mitochondrial function interference, glycolysis inhibition and macromolecular synthesis inhibition were illustrated in detail. Based on Chinese medicine principles, a better view of anti-tumor molecular mechanism of Chinese medicine from metabolic regulation perspective was obtained. Meanwhile a communal potential of solution for other anti-tumor drugs, anti-diabetes drugs and cholesterol reducing drugs was stimulated to explore further. The regulation of berberine on cancer cells reprogramming metabolism would also be benefit for therapeutic effect enhancement and side-effect alleviation, as well as a reference for individualized therapy in cancer treatment.

Issue date

2012

Author

Tan, Wen

Faculty

Institute of Chinese Medical Sciences

Degree

Ph.D.

Subject

Medicinal plants -- China

Herbs -- Therapeutic use -- China

Cell metabolism

Cancer -- Treatment

Antineoplastic agents

Biomedical Sciences -- Institute of Chinese Medical Sciences

Supervisor

王一濤

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Location
1/F Zone C
Library URL
991002084159706306