Ginsenosides, potent inhibitors of sialyltransferase

Wenxin Huang
  • Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Baojian Road 157, Nangang District, Harbin 150081, P.R. China
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, Liwen Sun
  • Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Baojian Road 157, Nangang District, Harbin 150081, P.R. China
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, Baihui Wang
  • Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Baojian Road 157, Nangang District, Harbin 150081, P.R. China
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, Yan Ma
  • Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Baojian Road 157, Nangang District, Harbin 150081, P.R. China
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, Dahong Yao
  • Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Baojian Road 157, Nangang District, Harbin 150081, P.R. China
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, Weina Han
  • Corresponding author
  • Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Baojian Road 157, Nangang District, Harbin 150081, P.R. China
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and Libo Wang
  • Corresponding author
  • Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Baojian Road 157, Nangang District, Harbin 150081, P.R. China
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Abstract

The overexpression of sialic acids and sialyltransferases (STs) during malignant transformation and progression could result in the aberrant sialylation of cancer cells. Therefore, interfering the sialic acid synthesis might be an effective pathway in cancer therapy. In this study, we assessed that the antitumor inhibitors of 20(S)-ginsenosides Rg3, 20(R)-ginsenosides Rg3, 20(S)-ginsenosides Rh2, and 20(R)-ginsenosides Rh2 could block the sialoglycans in liver cancer cells HepG2. The results showed that these four compounds could inhibit the expressions of the total and free sialic acid at different levels in HepG2, respectively; also, it showed dose dependence. In addition, the results of the enzyme-linked immunosorbent assay showed that the above four compounds can inhibit the expression of STs significantly. We also found that these compounds could mediate the block of sialylation of α2,3- and α2,6-linked sialic acids in HepG2 cells by flow cytometry. Meanwhile, the results of the molecular docking investigation showed that these compounds showed strong interaction with ST6GalI and ST3GalI. These results verified that the ginsenosides have a powerful inhibiting aberrant sialylation, and it laid a theoretical foundation for further research on the investigation of ginsenosides as the target inhibitors on STs.

  • 1.

    Wang L, Wang D, Zhou X, Wu L, Sun X. Systemic investigation on quinoxaline derivatization of sialic acids and their quantitation applicability using high performance liquid chromatography. RSC Adv 2014;4:45797–803.

  • 2.

    Varki A. Glycan-based interactions involving vertebrate sialic-acid-recognizing proteins. Nature 2007;446:1023–9.

  • 3.

    Crespo HJ, Lau JT, Videira PA. Dendritic cells: a spot on sialic acid. Front Immunol 2013;4:1–17.

  • 4.

    Harduin-Lepers A, Vallejo-Ruiz V, Krzewinski-Recchi MA, Samyn-Petit B, Julien S, Delannoy P. The human sialyltransferase family. Biochimie 2001;83:727–37.

  • 5.

    Li Y, Chen X. Sialic acid metabolism and sialyltransferases: natural functions and applications. Appl Microbiol Biotechnol 2012;94:887–905.

  • 6.

    Wang L, Liu Y, Wu L, Sun X. Sialyltransferases inhibition and recent advances. BBA-Proteins Proteom 2016;1864:143–53.

  • 7.

    Jones MB, Nasirikenari M, Feng L, Migliore MT, Choi KS, Kazim L. Role for hepatic and circulatory ST6Gal-1 sialyltransferase in regulating myelopoiesis. J Biol Chem 2010;285:25009–17.

  • 8.

    Cabral MG, Piteira AR, Silva Z, Ligeiro D, Brossmer R, Videira PA. Human dendritic cells contain surface sialyltransferase activity. Immunol Lett 2010;131:89–96.

  • 9.

    Szabo R, Skropeta D. Advancement of sialyltransferase inhibitors: therapeutic challenges and opportunities. Med Res Rev 2017;37:219–70.

  • 10.

    Dalziel M, Dall’Olio F, Mungul A, Piller V, Piller F. Ras oncogene induces betagalactoside α2,6-sialyltransferase (ST6Gal I) via a RalGEF mediated signal to its housekeeping promoter. Eur J Biochem 2004;271:3623–4.

  • 11.

    Fuster MM, Esko JD. The sweet and sour of cancer: glycans as novel therapeutic targets. Nat Rev Cancer 2005;5:526–42.

  • 12.

    Park JJ, Yi JY, Jin YB, Lee YJ, Lee JS, Lee YS. Sialylation of epidermal growth factor receptor regulates receptor activity and chemosensitivity to gefitinib in colon cancer cells. Biochem Pharmacol 2012;83:849–57.

  • 13.

    Jung KH, Schworer R, Schmidt RR. Sialyltransferase inhibitors. Trends Glycosci Glycotechnol 2003;15:275–89.

  • 14.

    Wang X, Zhang LH, Ye XS. Recent development in the design of sialyltransferase inhibitors. Med Res Rev 2003;23:32–47.

  • 15.

    Iza M, Wall MM, Heimberg RG, Rodebaugh TL, Schneier FR, Liu SM, et al. Latent structure of social fears and social anxiety disorders. Psychol Med 2014;44:361–70.

  • 16.

    Cheong JH, Kim H, Hong MJ, Yang MH, Kim JW, Yoo H, et al. Stereoisomer-specific anticancer activities of ginsenoside Rg3 and Rh2 in HepG2 cells: disparity in cytotoxicity and autophagy-inducing effects due to 20(S)-epimers. Biol Pharm Bull 2015;38:102–8.

  • 17.

    Kim JW, Jung SY, Kwon YH, Lee JH, Lee YM, Lee BY. Ginsenoside Rg3 attenuates tumor angiogenesis via inhibiting bioactivities of endothelial progenitor cells. Cancer Biol Ther 2012;13:504–15.

  • 18.

    Kikuchi Y, Sasa H, Kita T, Hirata J, Tode T, Nagata I. Inhibition of human ovarian cancer cell proliferation in vitro by ginsenoside Rh2 and adjuvant effects to cisplatin in vivo. Anticancer Drugs 1991;2:63–7.

  • 19.

    Tang XP, Tang GD, Fang CY, Liang ZH, Zhang LY. Effects of ginsenoside Rh2 on growth and migration of pancreatic cancer cells. World J Gastroenterol 2013;19:1582–92.

  • 20.

    Choi S, Oh JY, Kim SJ. Ginsenoside Rh2 induces Bcl-2 family proteins-mediated apoptosis in vitro and in xenografts in vivo models. J Cell Biochem 2011;112:330–40.

  • 21.

    Christian B, Thomas JB, Melissa W, de Graaf Annemarie MA, van Delft Floris L, den Brok Martijn H, et al. Targeting aberrant sialylation in cancer cells using a fluorinated sialic acid analog impairs adhesion, migration, and in vivo tumor growth. Mol Cancer Ther 2013;12:1935–46.

  • 22.

    Matthew SM, Britni MA, Cory DR, Poh-Choo P, Nikki B, Maria CG, et al. Systemic blockade of sialylation in ice with a global inhibitor of sialyltransferases. J Biol Chem 2014;289:35149–58.

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A Journal of Biosciences: Zeitschrift für Naturforschung C (ZNC) is an international scientific journal for the emerging field of natural and natural-like products. ZNC publishes original research on the isolation, bio-chemical synthesis and bioactivities of natural products, their biochemistry, pharmacology, biotechnology, and biological activity and innovative developed computational methods for predicting their structure and/or function.

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