Molecular Biology Reports

, Volume 46, Issue 4, pp 3857–3864 | Cite as

A metabolic investigation of anticancer effect of G. glabra root extract on nasopharyngeal carcinoma cell line, C666-1

  • Chaopan Zheng
  • Ling Han
  • Shihai WuEmail author
Original Article


Although a majority of nasopharyngeal carcinoma (NPC) are undifferentiated and strongly radiosensitive, many NPC patients still have troubles in recurrence. Traditional Chinese medicine (TCM) is considered as potential therapeutic drugs in NPC. However, the effect of Glycyrrhiza glabra on NPC is limited. The present study shows the decreased proliferation and high apoptosis in G. glabra root extract-treated C666-1 cells, indicating the anti-cancerous function of G. glabra in NPC. Then GC/MS-based metabolomics is employed to characterize variation of metabolomes in response to G. glabra root extract treatment. Metabolic category elaborates the higher percentage of down-regulated amino acids and lipids after G. glabra treatment. Moreover, ICA and pathway enrichment analysis further observe that glycine, serine and threonine metabolism, fatty acid biosynthesis, alanine, aspartate and glutamate metabolism, and cysteine and methionine metabolism are four important amino acid and lipid metabolisms that likely contribute to the anti-cancer effect of G. glabra in NPC. These pathways point out the seven metabolite biomarkers, glutathione, glutamine, l-alanine, glycine, l-serine, tetradecanoic acid and stearic acid. Taken together, these findings provide potential clues that anti-cancer mechanisms of G. glabra root extract are linked to the metabolic strategies and emphasize the significance of metabolic strategies against NPC.


Nasopharyngeal carcinoma G. glabra Metabolic regulation Amino acid Fatty acid 



This work was sponsored by grants from National Natural Science Foundation of China (CN) (No. N31801160).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    De Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, Forman D, Plummer M (2012) Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol 13(6):607–615PubMedGoogle Scholar
  2. 2.
    Cho WC, Chen HY (2009) Clinical efficacy of traditional Chinese medicine as a concomitant therapy for nasopharyngeal carcinoma: a systematic review and meta-analysis. Cancer Invest 27(3):334–344PubMedGoogle Scholar
  3. 3.
    Yin SY, Wei WC, Jian FY, Yang NS (2013) Therapeutic applications of herbal medicines for cancer patients. Evid Based Complement Alternat Med. PubMedPubMedCentralGoogle Scholar
  4. 4.
    Yanwei L, Yinli Y, Pan Z (2018) Traditional herbal formula NPC01 exerts antiangiogenic effects through inhibiting the PI3K/Akt/mTOR signaling pathway in nasopharyngeal carcinoma cells. Evid Based Complement Alternat Med. PubMedPubMedCentralGoogle Scholar
  5. 5.
    Zhao M, Luo C, Long F, Chen J, Tang L (1988) Growth capability of epithelial cell line of human poorly differentiated nasopharyngeal carcinoma and its response to Chinese medicinal herbs and marine drugs. Zhonghua Zhong Liu Za Zhi [Chin J Oncol] 10(2):98–101Google Scholar
  6. 6.
    Chien CR, Su SY, Cohen L, Lin HW, Lee RT, Shih YCT (2012) Use of Chinese medicine among survivors of nasopharyngeal carcinoma in taiwan: a population-based study. Integr Cancer Ther 11(3):221–231PubMedGoogle Scholar
  7. 7.
    Kim W, Lee WB, Lee J, Min BI, Lee H, Cho SH (2015) Traditional herbal medicine as adjunctive therapy for nasopharyngeal cancer: a systematic review and meta-analysis. Integr Cancer Ther 14(3):212–220PubMedGoogle Scholar
  8. 8.
    Nourazarian SM, Nourazarian A, Majidinia M, Roshaniasl E (2016) Effect of root extracts of medicinal herb Glycyrrhiza glabra on HSP90 gene expression and apoptosis in the HT-29 colon cancer cell line. Asian Pac J Cancer Prev 16(18):8563–8566Google Scholar
  9. 9.
    Shandiz S, Ataollah S, Salehzadeh A, Ahmadzadeh M, Khalatbari K (2017) Evaluation of cytotoxicity activity and NM23 gene expression in T47D breast cancer cell line treated with Glycyrrhiza glabra extract. J Genet Resour 3(1):47–53Google Scholar
  10. 10.
    Sun H, Zhang A, Yan G, Piao C, Li W, Sun C, Wu X, Li X, Chen Y, Wang X (2013) Metabolomic analysis of key regulatory metabolites in hepatitis C virus–infected tree shrews. Mol Cell Proteomics 12(3):710–719PubMedGoogle Scholar
  11. 11.
    Kuehnbaum NL, Britz-McKibbin P (2013) New advances in separation science for metabolomics: resolving chemical diversity in a post-genomic era. Chem Rev 113(4):2437–2468PubMedGoogle Scholar
  12. 12.
    Besada C, Sanchez G, Salvador A, Granell A (2013) Volatile compounds associated to the loss of astringency in persimmon fruit revealed by untargeted GC–MS analysis. Metabolomics 9(1):157–172Google Scholar
  13. 13.
    Chen XH, Liu SR, Peng B, Li D, Cheng ZX, Zhu JX, Zhang S, Peng YM, Li H, Zhang TT (2017) Exogenous l-valine promotes phagocytosis to kill multidrug-resistant bacterial pathogens. Front Immunol 8:207PubMedPubMedCentralGoogle Scholar
  14. 14.
    Fiehn O (2008) Extending the breadth of metabolite profiling by gas chromatography coupled to mass spectrometry. TrAC Trends Anal Chem 27(3):261–269Google Scholar
  15. 15.
    Chen XH, Zhang BW, Li H, Peng XX (2015) Myo-inositol improves the host’s ability to eliminate balofloxacin-resistant Escherichia coli. Sci Rep 5:10720PubMedPubMedCentralGoogle Scholar
  16. 16.
    Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y (2009) Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 457(7231):910PubMedPubMedCentralGoogle Scholar
  17. 17.
    Amathieu R, Nahon P, Triba M, Bouchemal N, Trinchet JC, Beaugrand M, Dhonneur G, Le Moyec L (2011) Metabolomic approach by 1H NMR spectroscopy of serum for the assessment of chronic liver failure in patients with cirrhosis. J Proteome Res 10(7):3239–3245PubMedGoogle Scholar
  18. 18.
    Naccarato WF, Ray RE, Wells WW (1974) Biosynthesis of myo-inositol in rat mammary gland. Isolation and properties of the enzymes. Arch Biochem Biophys 164(1):194–201PubMedGoogle Scholar
  19. 19.
    Wienkoop S, Morgenthal K, Wolschin F, Scholz M, Selbig J, Weckwerth W (2008) Integration of metabolomic and proteomic phenotypes analysis of data covariance dissects starch and RFO metabolism from low and high temperature compensation response in Arabidopsis thaliana. Mol Cell Proteomics 7(9):1725–1736PubMedPubMedCentralGoogle Scholar
  20. 20.
    Dong S, Inoue A, Zhu Y, Tanji M, Kiyama R (2007) Activation of rapid signaling pathways and the subsequent transcriptional regulation for the proliferation of breast cancer MCF-7 cells by the treatment with an extract of Glycyrrhiza glabra root. Food Chem Toxicol 45(12):2470–2478PubMedGoogle Scholar
  21. 21.
    Sheela M, Ramakrishna M, Salimath BP (2006) Angiogenic and proliferative effects of the cytokine VEGF in Ehrlich ascites tumor cells is inhibited by Glycyrrhiza glabra. Int Immunopharmacol 6(3):494–498PubMedGoogle Scholar
  22. 22.
    Tang F, Xie C, Huang D, Wu Y, Zeng M, Yi L, Wang Y, Mei W, Cao Y, Sun L (2011) Novel potential markers of nasopharyngeal carcinoma for diagnosis and therapy. Clin Biochem 44(8–9):711–718PubMedGoogle Scholar
  23. 23.
    Yi L, Dong N, Shi S, Deng B, Yun Y, Yi Z, Zhang Y (2014) Metabolomic identification of novel biomarkers of nasopharyngeal carcinoma. RSC Adv 4(103):59094–59101Google Scholar
  24. 24.
    Daye D, Wellen KE (2012) Metabolic reprogramming in cancer: unraveling the role of glutamine in tumorigenesis. Sem Cell Dev Biol. 23(4):362–369Google Scholar
  25. 25.
    Hensley CT, Wasti AT, DeBerardinis RJ (2013) Glutamine and cancer: cell biology, physiology, and clinical opportunities. J Clin Invest 123(9):3678–3684PubMedPubMedCentralGoogle Scholar
  26. 26.
    Wise DR, Thompson CB (2010) Glutamine addiction: a new therapeutic target in cancer. Trends Biochem Sci 35(8):427–433PubMedPubMedCentralGoogle Scholar
  27. 27.
    Lan J, Tai HC, Lee SW, Chen TJ, Huang HY, Li CF (2014) Deficiency in expression and epigenetic DNA methylation of ASS1 gene in nasopharyngeal carcinoma: negative prognostic impact and therapeutic relevance. Tumor Biol 35(1):161–169Google Scholar
  28. 28.
    DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, Thompson CB (2007) Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci 104(49):19345–19350PubMedGoogle Scholar
  29. 29.
    Gaglio D, Metallo CM, Gameiro PA, Hiller K, Danna LS, Balestrieri C, Alberghina L, Stephanopoulos G, Chiaradonna F (2011) Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth. Mol Syst Biol 7(1):523PubMedPubMedCentralGoogle Scholar
  30. 30.
    Semenza GL (2012) Hypoxia-inducible factors in physiology and medicine. Cell 148(3):399–408PubMedPubMedCentralGoogle Scholar
  31. 31.
    Altman BJ, Stine ZE, Dang CV (2016) From krebs to clinic: glutamine metabolism to cancer therapy. Nat Rev Cancer 16(10):619PubMedPubMedCentralGoogle Scholar
  32. 32.
    Ward PS, Patel J, Wise DR, Abdel-Wahab O, Bennett BD, Coller HA, Cross JR, Fantin VR, Hedvat CV, Perl AE (2010) The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17(3):225–234PubMedPubMedCentralGoogle Scholar
  33. 33.
    Welbourne T (1979) Ammonia production and glutamine incorporation into glutathione in the functioning rat kidney. Can J Biochem 57(3):233–237PubMedGoogle Scholar
  34. 34.
    Godwin AK, Meister A, O’Dwyer PJ, Huang CS, Hamilton TC, Anderson ME (1992) High resistance to cisplatin in human ovarian cancer cell lines is associated with marked increase of glutathione synthesis. Proc Natl Acad Sci 89(7):3070–3074PubMedGoogle Scholar
  35. 35.
    Ishimoto T, Nagano O, Yae T, Tamada M, Motohara T, Oshima H, Oshima M, Ikeda T, Asaba R, Yagi H (2011) CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc − and thereby promotes tumor growth. Cancer Cell 19(3):387–400PubMedGoogle Scholar
  36. 36.
    Timmerman LA, Holton T, Yuneva M, Louie RJ, Padró M, Daemen A, Hu M, Chan DA, Ethier SP, van‘t Veer LJ (2013) Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target. Cancer Cell 24(4):450–465PubMedPubMedCentralGoogle Scholar
  37. 37.
    Sousa CM, Biancur DE, Wang X, Halbrook CJ, Sherman MH, Zhang L, Kremer D, Hwang RF, Witkiewicz AK, Ying H (2016) Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. Nature 536(7617):479PubMedPubMedCentralGoogle Scholar
  38. 38.
    Kuhajda FP (2006) Fatty acid synthase and cancer: new application of an old pathway. Cancer Res 66(12):5977–5980PubMedGoogle Scholar
  39. 39.
    Menendez JA, Lupu R (2007) Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 7(10):763PubMedGoogle Scholar
  40. 40.
    Yang YA, Han WF, Morin PJ, Chrest FJ, Pizer ES (2002) Activation of fatty acid synthesis during neoplastic transformation: role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Exp Cell Res 279(1):80–90PubMedGoogle Scholar
  41. 41.
    Lv W, Yang T (2012) Identification of possible biomarkers for breast cancer from free fatty acid profiles determined by GC–MS and multivariate statistical analysis. Clin Biochem 45(1–2):127–133PubMedGoogle Scholar
  42. 42.
    Zeng L, Wu G-Z, Goh KJ, Lee YM, Ng CC, You AB, Wang J, Jia D, Hao A, Yu Q (2008) Saturated fatty acids modulate cell response to DNA damage: implication for their role in tumorigenesis. PLoS ONE 3(6):e2329PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Otorhinolaryngology, Shenzhen People’s HospitalThe Second Clinical Medical College of Jinan UniversityShenzhenChina
  2. 2.Department of Radiology, Shenzhen People’s HospitalThe Second Clinical Medical College of Jinan UniversityShenzhenChina

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