Generic placeholder image

Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

NMR-based Metabolomic Techniques Identify the Anticancer Effects of Three Polyphyllins in HepG2 Cells

Author(s): Feng Su*, Haibo Wang, Yifan Wang, Lv Ye, Peixi Zhu, Jinping Gu and Weike Su*

Volume 18, Issue 4, 2022

Published on: 23 August, 2021

Page: [415 - 426] Pages: 12

DOI: 10.2174/1573412917666210823090145

Price: $65

Open Access Journals Promotions 2
Abstract

Background Rhizoma paridis (RP) is a traditional Chinese herb used for the treatment of tumors, detoxification and hemostasia. Studies show the main components of RP are Polyphyllin I (PPI), polyphyllin VI (PPVI), and polyphyllin VII (PPVII). However, the pharmaco-mechanisms of these compounds are not clear.

Objectives: By used 1H nuclear magnetic resonance (1H-NMR) based metabolomics approach to identify the Anticancer effects of PPI, PPVI and PPVII in HepG2 cells.

Methods 1H nuclear magnetic resonance (1H-NMR) based metabolomics approach was applied to investigate the toxicological effect of PPI, PPVI, PPVII on HepG2 cells. Multivariate statistical analysis was employed to examine the metabolic changes and abnormal metabolic pathways, including Principal Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and orthogonal PLS-DA (OPLS-DA).

Results The results showed that the effects of metabolic phenotypes were affected separately by PPI, PPVI, and PPVII. The metabolic phenotypes were also changed over time. The characteristic metabolites were varied by affecting different polyphylins, which were identified by the reconstructed OPLSDA loading plots. According to the characteristic metabolites, the mainly disturbed metabolic pathways were found, such as alanine, aspartate and glutamate metabolism, pyruvate metabolism, glycine, serine, and threonine metabolism.

Conclusion The current work could allow us to understand the therapeutic effect of RP in metabolism. It also indicated that RP would be a promising candidate for liver cancer treatment.

Keywords: Polyphyllin, nuclear magnetic resonance, metabolomics, metabolic analysis, HepG2 cell, PCA.

Graphical Abstract
[1]
Lau, B.F.; Abdullah, N.; Aminudin, N.; Lee, H.B.; Tan, P.J. Ethnomedicinal uses, pharmacological activities, and cultivation of Lignosus spp. (tiger׳s milk mushrooms) in Malaysia - A review. J. Ethnopharmacol., 2015, 169, 441-458.
[http://dx.doi.org/10.1016/j.jep.2015.04.042] [PMID: 25937256]
[2]
Wang, N.; Tan, H.Y.; Chan, Y.T.; Guo, W.; Li, S.; Feng, Y. Identification of WT1 as determinant of heptatocellular carcinoma and its inhibition by Chinese herbal medicine Salvia chinensis Benth and its active ingredient protocatechualdehyde. Oncotarget, 2017, 8(62), 105848-105859.
[http://dx.doi.org/10.18632/oncotarget.22406] [PMID: 29285297]
[3]
Meng, Q.; Pan, J.; Liu, Y.; Chen, L.; Ren, Y. Anti-tumour effects of polysaccharide extracted from Acanthopanax senticosus and cell-mediated immunity. Exp. Ther. Med., 2018, 15(2), 1694-1701.
[PMID: 29434755]
[4]
Cheng, Z.X.; Liu, B.R.; Qian, X.P.; Ding, Y.T.; Hu, W.J.; Sun, J.; Yu, L.X. Proteomic analysis of anti-tumor effects by Rhizoma Paridis total saponin treatment in HepG2 cells. J. Ethnopharmacol., 2008, 120(2), 129-137.
[http://dx.doi.org/10.1016/j.jep.2008.07.030] [PMID: 18761071]
[5]
Sun, J.; Liu, B.R.; Hu, W.J.; Yu, L.X.; Qian, X.P. In vitro anticancer activity of aqueous extracts and ethanol extracts of fifteen traditional Chinese medicines on human digestive tumor cell lines. Phytother. Res., 2007, 21(11), 1102-1104.
[http://dx.doi.org/10.1002/ptr.2196] [PMID: 17639550]
[6]
Man, S.; Gao, W.; Zhang, Y.; Yan, L.; Ma, C.; Liu, C.; Huang, L. Antitumor and antimetastatic activities of Rhizoma Paridis saponins. Steroids, 2009, 74(13-14), 1051-1056.
[http://dx.doi.org/10.1016/j.steroids.2009.08.004] [PMID: 19699217]
[7]
Chan, J.Y.W.; Koon, J.C.M.; Liu, X.; Detmar, M.; Yu, B.; Kong, S.K.; Fung, K.P. Polyphyllin D, a steroidal saponin from Paris polyphylla, inhibits endothelial cell functions in vitro and angiogenesis in zebrafish embryos in vivo. J. Ethnopharmacol., 2011, 137(1), 64-69.
[http://dx.doi.org/10.1016/j.jep.2011.04.021] [PMID: 21658438]
[8]
Chang, J.; Wang, H.; Wang, X.; Zhao, Y.; Zhao, D.; Wang, C.; Li, Y.; Yang, Z.; Lu, S.; Zeng, Q.; Zimmerman, J.; Shi, Q.; Wang, Y.; Yang, Y. Molecular mechanisms of Polyphyllin I-induced apoptosis and reversal of the epithelial-mesenchymal transition in human osteosarcoma cells. J. Ethnopharmacol., 2015, 170, 117-127.
[http://dx.doi.org/10.1016/j.jep.2015.05.006] [PMID: 25978954]
[9]
Song, S.; Du, L.; Jiang, H.; Zhu, X.; Li, J.; Xu, J. Paris Saponin I Sensitizes Gastric Cancer Cell Lines to Cisplatin via Cell Cycle Arrest and Apoptosis. Med. Sci. Monit., 2016, 22, 3798-3803.
[http://dx.doi.org/10.12659/MSM.898232] [PMID: 27755523]
[10]
Yang, Q.; Chen, W.; Xu, Y.; Lv, X.; Zhang, M.; Jiang, H. Polyphyllin I modulates MALAT1/STAT3 signaling to induce apoptosis in gefitinib-resistant non-small cell lung cancer. Toxicol. Appl. Pharmacol., 2018, 356, 1-7.
[http://dx.doi.org/10.1016/j.taap.2018.07.031] [PMID: 30076870]
[11]
Feng, F.F.; Cheng, P.; Sun, C.; Wang, H.; Wang, W. Inhibitory effects of polyphyllins I and VII on human cisplatin-resistant NSCLC via p53 upregulation and CIP2A/AKT/mTOR signaling axis inhibition. Chin. J. Nat. Med., 2019, 17(10), 768-777.
[http://dx.doi.org/10.1016/S1875-5364(19)30093-7] [PMID: 31703757]
[12]
Pang, D.J.; Li, C.; Yang, C.C.; Zou, Y.F.; Feng, B.; Li, L.X.; Liu, W.T.; Geng, Y.; Luo, Q.H.; Chen, Z.L.; Huang, C. Polyphyllin VII promotes apoptosis and autophagic cell death via ROS-inhibited AKT activity, and sensitizes glioma cells to temozolomide; Oxidative Med Cell Longev, 2019, p. p. 1805635.
[13]
Tian, Y.; Jia, S.X.; Shi, J.; Gong, G.Y.; Yu, J.W.; Niu, Y.; Yang, C.M.; Ma, X.C.; Fang, M.Y. Polyphyllin I induces apoptosis and autophagy via modulating JNK and mTOR pathways in human acute myeloid leukemia cells. Chem. Biol. Interact., 2019, 311108793
[http://dx.doi.org/10.1016/j.cbi.2019.108793] [PMID: 31421117]
[14]
Villanueva, A. Hepatocellular Carcinoma. N. Engl. J. Med., 2019, 380(15), 1450-1462.
[http://dx.doi.org/10.1056/NEJMra1713263] [PMID: 30970190]
[15]
Jordan, K.W.; Nordenstam, J.; Lauwers, G.Y.; Rothenberger, D.A.; Alavi, K.; Garwood, M.; Cheng, L.L. Metabolomic characterization of human rectal adenocarcinoma with intact tissue magnetic resonance spectroscopy. Dis. Colon Rectum, 2009, 52(3), 520-525.
[http://dx.doi.org/10.1007/DCR.0b013e31819c9a2c] [PMID: 19333056]
[16]
Hall, R.D.; Brouwer, I.D.; Fitzgerald, M.A. Plant metabolomics and its potential application for human nutrition. Physiol. Plant., 2008, 132(2), 162-175.
[PMID: 18251858]
[17]
Duarte, I.F. Following dynamic biological processes through NMR-based metabonomics: a new tool in nanomedicine? J. Control. Release, 2011, 153(1), 34-39.
[http://dx.doi.org/10.1016/j.jconrel.2011.03.008] [PMID: 21406205]
[18]
Vignoli, A.; Ghini, V.; Meoni, G.; Licari, C.; Takis, P.G.; Tenori, L.; Turano, P.; Luchinat, C. High-throughput metabolomics by 1D NMR. Angew. Chem. Int. Ed. Engl., 2019, 58(4), 968-994.
[http://dx.doi.org/10.1002/anie.201804736] [PMID: 29999221]
[19]
Lindon, J.C.; Nicholson, J.K. Spectroscopic and statistical techniques for information recovery in metabonomics and metabolomics. Annu. Rev. Anal. Chem., 2008, 1, 45-69.
[20]
Brennan, L. NMR-based metabolomics: from sample preparation to applications in nutrition research. Prog. Nucl. Magn. Reson. Spectrosc., 2014, 83, 42-49.
[http://dx.doi.org/10.1016/j.pnmrs.2014.09.001] [PMID: 25456316]
[21]
Zhao, L.; Hu, J.; Huang, Y.; Wang, H.; Adeleye, A.; Ortiz, C.; Keller, A.A. 1H NMR and GC-MS based metabolomics reveal nano-Cu altered cucumber (Cucumis sativus) fruit nutritional supply. Plant Physiol. Biochem., 2017, 110, 138-146.
[http://dx.doi.org/10.1016/j.plaphy.2016.02.010] [PMID: 26922143]
[22]
Gu, J.; Shu, D.; Su, F.; Xie, Y.; Liang, X. Analysis of metabolome changes in the HepG2 cells of apatinib treatment by using the NMR-based metabolomics. J. Cell. Biochem., 2019, 120(11), 19137-19146.
[http://dx.doi.org/10.1002/jcb.29242] [PMID: 31264262]
[23]
Jia, H.M.; Feng, Y.F.; Liu, Y.T.; Chang, X.; Chen, L.; Zhang, H.W.; Ding, G.; Zou, Z.M. Integration of H-1 NMR and UPLC-Q-TOF/MS for a comprehensive urinary metabonomics study on a rat model of depression induced by chronic unpredictable mild stress. PLoS One, 2013, 8(5), 11.
[http://dx.doi.org/10.1371/journal.pone.0063624]
[24]
Zhang, P.; Zhu, S.; Zhao, M.; Dai, Y.; Zhang, L.; Ding, S.; Zhao, P.; Li, J. Integration of 1H NMR- and UPLC-Q-TOF/MS-based plasma metabonomics study to identify diffuse axonal injury biomarkers in rat. Brain Res. Bull., 2018, 140, 19-27.
[http://dx.doi.org/10.1016/j.brainresbull.2018.03.012] [PMID: 29605486]
[25]
Pontes, J.G.M.; Brasil, A.J.M.; Cruz, G.C.F.; De Souza, R.N.; Tasic, L. NMR-based metabolomics strategies: plants, animals and humans. Anal. Methods, 2017, 9(7), 1078-1096.
[http://dx.doi.org/10.1039/C6AY03102A]
[26]
Zhang, L.; Wang, L.; Hu, Y.; Liu, Z.; Tian, Y.; Wu, X.; Zhao, Y.; Tang, H.; Chen, C.; Wang, Y. Selective metabolic effects of gold nanorods on normal and cancer cells and their application in anticancer drug screening. Biomaterials, 2013, 34(29), 7117-7126.
[http://dx.doi.org/10.1016/j.biomaterials.2013.05.043] [PMID: 23787109]
[27]
Chen, C.; Gao, J.; Wang, T.S.; Guo, C.; Yan, Y.J.; Mao, C.Y.; Gu, L.W.; Yang, Y.; Li, Z.F.; Liu, A. NMR-based metabolomic techniques identify the toxicity of emodin in HepG2 cells. Sci. Rep., 2018, 8(1), 9379.
[http://dx.doi.org/10.1038/s41598-018-27359-4] [PMID: 29925852]
[28]
Wolfender, J.L.; Nuzillard, J.M.; van der Hooft, J.J.J.; Renault, J.H.; Bertrand, S. Accelerating metabolite identification in natural product research: toward an ideal combination of liquid chromatography-high-resolution tandem mass spectrometry and NMR profiling, in silico databases, and chemometrics. Anal. Chem., 2019, 91(1), 704-742.
[http://dx.doi.org/10.1021/acs.analchem.8b05112] [PMID: 30453740]
[29]
Seger, C.; Sturm, S.; Stuppner, H. Mass spectrometry and NMR spectroscopy: modern high-end detectors for high resolution separation techniques--state of the art in natural product HPLC-MS, HPLC-NMR, and CE-MS hyphenations. Nat. Prod. Rep., 2013, 30(7), 970-987.
[http://dx.doi.org/10.1039/c3np70015a] [PMID: 23739842]
[30]
Gu, Jinping; Dan, Shu; Feng, Su; Xie, Yuanyuan Liang, Xianrui Analysis of metabolome changes in the HepG2 cells of apatinib treatment by using the NMR-based metabolomics. 2019, 120(11), 19137-19146.
[31]
Craig, A.; Cloarec, O.; Holmes, E.; Nicholson, J.K.; Lindon, J.C. Scaling and normalization effects in NMR spectroscopic metabonomic data sets. Anal. Chem., 2006, 78(7), 2262-2267.
[http://dx.doi.org/10.1021/ac0519312] [PMID: 16579606]
[32]
Cloarec, O.; Dumas, M.E.; Trygg, J.; Craig, A.; Barton, R.H.; Lindon, J.C.; Nicholson, J.K.; Holmes, E. Evaluation of the orthogonal projection on latent structure model limitations caused by chemical shift variability and improved visualization of biomarker changes in 1H NMR spectroscopic metabonomic studies. Anal. Chem., 2005, 77(2), 517-526.
[http://dx.doi.org/10.1021/ac048803i] [PMID: 15649048]
[33]
Wang, H.; Tso, V.K.; Slupsky, C.M.; Fedorak, R.N. Metabolomics and detection of colorectal cancer in humans: a systematic review. Future Oncol., 2010, 6(9), 1395-1406.
[http://dx.doi.org/10.2217/fon.10.107] [PMID: 20919825]
[34]
Chong, J.; Soufan, O.; Li, C.; Caraus, I.; Li, S.; Bourque, G.; Wishart, D.S.; Xia, J. MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis. Nucleic Acids Res., 2018, 46(W1), W486-W494.
[http://dx.doi.org/10.1093/nar/gky310] [PMID: 29762782]
[35]
Gu, J.; Su, F.; Hong, P.; Zhang, Q.; Zhao, M. 1H NMR-based metabolomic analysis of nine organophosphate flame retardants metabolic disturbance in Hep G2 cell line. Sci. Total Environ., 2019, 665, 162-170.
[http://dx.doi.org/10.1016/j.scitotenv.2019.02.055] [PMID: 30772545]
[36]
Malik, M.; Chaudhary, R.; Pundir, C.S. An improved enzyme nanoparticles based amperometric pyruvate biosensor for detection of pyruvate in serum. Enzyme Microb. Technol., 2019, 123, 30-38.
[http://dx.doi.org/10.1016/j.enzmictec.2019.01.006] [PMID: 30686348]
[37]
Viana, L.R.; Canevarolo, R.; Luiz, A.C.P.; Soares, R.F.; Lubaczeuski, C.; Zeri, A.C.D.; Gomes-Marcondes, M.C.C. Leucine-rich diet alters the 1H-NMR based metabolomic profile without changing the Walker-256 tumour mass in rats. BMC Cancer, 2016, 16(1), 764.
[http://dx.doi.org/10.1186/s12885-016-2811-2] [PMID: 27716121]
[38]
Ippolito, L.; Morandi, A.; Giannoni, E.; Chiarugi, P. Lactate: A metabolic driver in the tumour landscape. Trends Biochem. Sci., 2019, 44(2), 153-166.
[http://dx.doi.org/10.1016/j.tibs.2018.10.011] [PMID: 30473428]
[39]
Feng, J.H.; Zhao, J.; Hao, F.H.; Chen, C.; Bhakoo, K.; Tang, H.R. NMR-based metabonomic analyses of the effects of ultrasmall superparamagnetic particles of iron oxide (USPIO) on macrophage metabolism. J. Nanopart. Res., 2011, 13(5), 2049-2062.
[http://dx.doi.org/10.1007/s11051-010-9959-5]
[40]
Jain, M.; Nilsson, R.; Sharma, S.; Madhusudhan, N.; Kitami, T.; Souza, A.L.; Kafri, R.; Kirschner, M.W.; Clish, C.B.; Mootha, V.K. Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science, 2012, 336(6084), 1040-1044.
[http://dx.doi.org/10.1126/science.1218595] [PMID: 22628656]
[41]
Garcia, A.R.; Arsenian-Henriksson, M. Serine-glycine-one-carbon metabolism: The hidden achilles heel of MYCN-amplified neuroblastoma? Cancer Res., 2019, 79(15), 3818-3819.
[http://dx.doi.org/10.1158/0008-5472.CAN-19-1816] [PMID: 31371280]
[42]
Olin-Sandoval, V.; Yu, J.S.L.; Miller-Fleming, L.; Alam, M.T.; Kamrad, S.; Correia-Melo, C.; Haas, R.; Segal, J.; Peña Navarro, D.A.; Herrera-Dominguez, L.; Méndez-Lucio, O.; Vowinckel, J.; Mülleder, M.; Ralser, M. Lysine harvesting is an antioxidant strategy and triggers underground polyamine metabolism. Nature, 2019, 572(7768), 249-253.
[http://dx.doi.org/10.1038/s41586-019-1442-6] [PMID: 31367038]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy