Effects of glaucocalyxin A on human liver cancer cells as revealed by GC/MS- and LC/MS-based metabolic profiling
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Studies have documented the potential antitumor activities of glaucocalyxin A (GLA), an ent-kaurene diterpenoid isolated from Rabdosia japonica. However, the metabolic mechanism underlying the antitumor activity of GLA remains largely unknown. The effects of GLA on the metabolome of human liver cancer cells using GC/MS- and LC/MS-based metabolic profiling have been investigated. An untargeted metabolomics approach in conjunction with orthogonal projection to latent structures–discriminant analysis (OPLS-DA) has been developed to characterize the metabolic modifications induced by GLA treatment in human hepatoma cell line SMMC7721. Results demonstrated that cells cultured in the presence or absence of GLA displayed different metabolic profiles: the treatment induced an increased purine metabolism, pyrimidine metabolism, and sphingolipid metabolism and a decreased amino acid metabolism. At the same time, GLA treatment induced cell apoptosis and cell cycle arrested at G2/M phase in a dose-dependent manner. In addition, two representative apoptosis-inducing cytotoxic agents were selected as positive control drugs to validate the reasonableness and accuracy of our metabolomic investigation on GLA. The study displayed a systemic metabolic alteration induced by GLA treatment, showing the impaired physiological activity of SMMC7721 cells, which also indicated anti-proliferative and apoptotic effects of GLA. In the meantime, GC/MS- and LC/MS-based metabolomics applied to cell culture enhanced our current understanding of the metabolic response to GLA treatment and its mechanism; such an approach could be transferred to study the mechanism of other anticancer drugs.
KeywordsGlaucocalyxin A Human liver cancer cell Gas chromatography–mass spectrometry Liquid chromatography–mass spectrometry Metabolic profiling Metabolomics
The authors appreciate the financial support from Shanghai Sailing Program (No.17YF1424700), National Natural Science Foundation of China (No. 8157131073, No. 81703674), and Shanghai Science and technology innovation action plan (No. 15401900700).
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Conflict of interest
The authors declare that they have no conflict of interest.
- 3.Xiang Z, Wu X, Liu X, Jin Y. Glaucocalyxin A: a review. Nat Prod Res. 2014; https://doi.org/10.1080/14786419.2014.934235:1-16.
- 17.Lei S, Huang F, Zhao A, Chen T, Chen W, Xie G, et al. The ratio of dihomo-γ-linolenic acid to deoxycholic acid species is a potential biomarker for the metabolic abnormalities in obesity. FASEB J. 2017; https://doi.org/10.1096/fj.201700055R.
- 18.Chen T, Xie G, Wang X, Fan J, Qiu Y, Zheng X et al. Serum and urine metabolite profiling reveals potential biomarkers of human hepatocellular carcinoma. Mol Cell Proteomics. 2011;10(7):M110.004945.Google Scholar
- 19.Tan Y, Yin P, Tang L, Xing W, Huang Q, Cao D et al. Metabolomics study of stepwise hepatocarcinogenesis from the model rats to patients: potential biomarkers effective for small hepatocellular carcinoma diagnosis. Mol Cell Proteomics. 2012;11(2):M111.010694.Google Scholar
- 20.Li Y, Ruan Q, Li Y, Ye G, Lu X, Lin X, et al. A novel approach to transforming a non-targeted metabolic profiling method to a pseudo-targeted method using the retention time locking gas chromatography/mass spectrometry-selected ions monitoring. J Chromatogr A. 2012;1255:228–36.CrossRefGoogle Scholar
- 33.Ong ES, Zou L, Li S, Cheah PY, Eu KW, Ong CN. Metabolic profiling in colorectal cancer reveals signature metabolic shifts during tumorigenesis. Mol Cell Proteomics. 2010; https://doi.org/10.1074/mcp.M900551-MCP200.
- 39.Kohara H, Tabata M, Kiura K, Ueoka H, Kawata K, Chikamori M, et al. Synergistic effects of topoisomerase I inhibitor, 7-ethyl-10-hydroxycamptothecin, and irradiation in a cisplatin-resistant human small cell lung cancer cell line. Clin Cancer Res. 2002;8(1):287–92.Google Scholar
- 51.Smith MW, Yue ZN, Geiss GK, Sadovnikova NY, Carter VS, Boix L, et al. Identification of novel tumor markers in hepatitis C virus-associated hepatocellular carcinoma. Cancer Res. 2003;63(4):859–64.Google Scholar