title: Utilization of metabonomics to identify serum biomarkers in murine H22 hepatocarcinoma and deduce antitumor mechanism of Rhizoma Paridis saponins.
abstract: Murine H22 hepatocarcinoma model is so popular to be used for the preclinical anticancer candidate's evaluation. However, the metabolic biomarkers of this model were not identified. Meanwhile, Rhizoma Paridis saponins (RPS) as natural products have been found to show strong antitumor activity, while its anti-cancer mechanism is not clear. To search for potential metabolite biomarkers of this model, serum metabonomics approach was applied to detect the variation of metabolite biomarkers and the related metabolism genes and signaling pathway were used to deduce the antitumor mechanisms of RPS. As a result, ten serum metabolites were identified in twenty-four mice including healthy mice, non-treated cancer mice, RPS-treated cancer mice and RPS-treated healthy mice. RPS significantly decreased tumor weight correlates to down-regulating lactate, acetate, N-acetyl amino acid and glutamine signals (p < 0.05), which were marked metabolites screened according to the very important person (VIP), loading plot and receiver operating characteristic curve (ROC) tests. For the analysis of metabolic enzyme related genes, RPS reversed the aerobic glycolysis through activating tumor suppressor p53 and PTEN, and suppressed FASN to inhibit lipogenesis. What's more, RPS repressed Myc and GLS expression and decreased glutamine level. The regulating PI3K/Akt/mTOR and HIF-1α/Myc/Ras networks also participated in these metabolic changes. Taken together, RPS suppressed ATP product made the tumor growth slow, which indicated a good anti-cancer effect and new angle for understanding the mechanism of RPS. In conclusion, this study demonstrated that the utility of (1)H NMR metabolic profiles taken together with tumor weight and viscera index was a promising screening tool for evaluating the antitumor effect of candidates. In addition, RPS was a potent anticancer agent through inhibiting cancer cellular metabolism to suppress proliferation in hepatoma H22 tumor murine, which promoted the application of RPS in the future.
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
authors.forename: Peiyu
authors.initials: P
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China. Electronic address: msl@tust.edu.cn.
authors.forename: Shuli
authors.initials: S
authors.lastname: Man
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
authors.forename: He
authors.initials: H
authors.lastname: Yang
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, School of Pharmaceutical Science & Technology, Tianjin University, Tianjin, 300072, China. Electronic address: biochemgao@163.com.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Gao
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019684:Magnoliopsida / Q000737:chemistry; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D027343:Rhizome / Q000737:chemistry; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D004365:Drugs, Chinese Herbal; D012503:Saponins
keywords: Anti-cancer mechanism; H22 hepatocarcinoma murine; Marker metabolites; Metabonomics; Nuclear magnetic resonance; Rhizoma paridis saponins