Biomolecules & Therapeutics

  • 제20권6호
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  • Pages.499-505
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  • 2012
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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Targeting Nrf2-Mediated Gene Transcription by Triterpenoids and Their Derivatives

  • Loboda, Agnieszka (Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University) ;
  • Rojczyk-Golebiewska, Ewa (Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University) ;
  • Bednarczyk-Cwynar, Barbara (Department of Organic Chemistry, Faculty of Pharmacy, University of Medical Sciences) ;
  • Zaprutko, Lucjusz (Department of Organic Chemistry, Faculty of Pharmacy, University of Medical Sciences) ;
  • Jozkowicz, Alicja (Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University) ;
  • Dulak, Jozef (Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University)
  • 투고 : 2012.10.25
  • 심사 : 2012.11.09
  • 발행 : 2012.11.30
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초록

Chemoprevention represents a strategy designed to protect cells or tissues against various carcinogens and carcinogenic metabolites derived from exogenous or endogenous sources. Recent studies indicate that plant-derived triterpenoids, like oleanolic acid, may exert cytoprotective functions via regulation of the activity of different transcription factors. The chemopreventive effects may be mediated through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor. Activation of Nrf2 by triterpenoids induces the expression of phase 2 detoxifying and antioxidant enzymes such as NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) - proteins which can protect cells or tissues against various toxic metabolites. On the other hand, inhibition of other transcription factors, like NF-${\kappa}B$ leads to the decrease in the pro-inflammatory gene expression. Moreover, the modulation of microRNAs activity may constitute a new mechanism responsible for valuable effects of triterpenoids. Recently, based on the structure of naturally occurring triterpenoids and with involvement of bioinformatics and computational chemistry, many synthetic analogs with improved biological properties have been obtained. Data from in vitro and in vivo experiments strongly suggest synthetic derivatives as promising candidates in the chemopreventive and chemotherapeutic strategies.

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참고문헌

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