NMR Studies Of The Quercetin Effects On HepG2Cellular Metabonome

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, one of the most prevalent malignant tumor types and the third leading cause of cancer-related death worldwide. The current clinical treatment options for liver cancer, including liver resection surgery, intra-arterial chemotherapy, radiation therapy and drug treatment, but their outcome remains unsatisfactory. So scientists are working hard to solve the problem. To investigate the regulation of tumor cell proliferation, apoptosis and metabolic mechanism in hepatocarcinogenesis is of significance to science. Quercetin, an important flavonol, is reported to have obvious anti-proliferative effects on many tumor cell lines, but how quercetin effects on tumor cellular metabolism remains unclear.Therefore, in this thesis, the’H Nuclear Magnetic Resonance (NMR) spectroscopic techniques in conjunction with multivariate data analysis methods were employed to two aspects of metabonomic studies including the metabolic profiles of cell media and cell extracts which has been effected by quercetin with five dose groups.Research finds that quercetin has a prominent effect on HepG2cellular metabonome and the effect has obvious dose dependent. First,1H NMR showed that HepG2cellular metabonome mainly contained glucose and other carbohydrates, citric acid and succinate and other TCA cycle related metabolites, amino acids, metabolites of choline, fatty acid, pyrimidine and purine. Secondly, the results suggested that quercetin effects on HepG2cellular metabolism caused systems alterations in metabolic networks including gluconeogenesis/glycolysis, amino acid metabolism, cell membrane metabolism, lipid metabolism and nucleotide metabolism. Lastly, the effect was dose-dependent and with the dose increased, the effect was enhanced. These findings demonstrated the NMR-based metabonomic analysis as a powerful approach for understanding the molecular aspects of the effects of drug on cellular metabolism and provided some basic metabolic information to investigate the effect of quercetin on HepG2cells.