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2014-04-29 - Article/Dans un journal avec peer-review - Anglais - 9 page(s)

Charles Catherine, Nachtergael Amandine , Ouedraogo M., Belayew Alexandra , Duez Pierre , "Effects of chemopreventive natural products on non-homologous end-joining DNA double-strand break repair" in Mutation Research - Genetic Toxicology and Environmental Mutagenesis, 768, 33-41, http://dx.doi.org/10.1016/j.mrgentox.2014.04.014

  • Edition : Elsevier (Netherlands)
  • Codes CREF : Chimie analytique (DI1314), Pharmacognosie (DI3410), Sciences pharmaceutiques (DI3400), Sciences exactes et naturelles (DI1000), Toxicologie pharmaceutique (DI3440)
  • Unités de recherche UMONS : Biochimie métabolique et moléculaire (M122), Chimie thérapeutique et Pharmacognosie (M136)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)

Abstract(s) :

(Anglais) Double-strand breaks (DSBs) may result from endogenous (e.g., reactive oxygen species, variable (diversity) joining, meiotic exchanges, collapsed replication forks, nucleases) or exogenous (e.g., ionizing radiation, chemotherapeutic agents, radiomimetic compounds) events. DSBs disrupt the integrity of DNA and failed or improper DSBs repair may lead to genomic instability and, eventually, mutations, cancer, or cell death. Non-homologous end-joining (NHEJ) is the major pathway used by higher eukaryotic cells to repair these lesions. Given the complexity of NHEJ and the number of proteins and cofactors involved, secondary metabolites from medicinal or food plants might interfere with the process, activating or inhibiting repair. Twelve natural products, arbutin, curcumin, indole-3-carbinol, and nine flavonoids (apigenin, baicalein, chalcone, epicatechin, genistein, myricetin, naringenin, quercetin, sakuranetin) were chosen for their postulated roles in cancer chemoprevention and/or treatment. The effects of these compounds on NHEJ were investigated with an in vitro protocol based on plasmid substrates. Plasmids were linearized by a restriction enzyme, generating cohesive ends, or by a combination of enzymes, generating incompatible ends; plasmids were then incubated with a nuclear extract prepared from normal human small-intestinal cells (FHS 74 Int), either treated with these natural products or untreated (controls). The NHEJ repair complex from nuclear extracts ligates linearized plasmids, resulting in plasmid oligomers that can be separated and quantified by on-chip microelectrophoresis. Some compounds (chalcone, epicatechin, myricetin, sakuranetin and arbutin) clearly activated NHEJ, whereas others (apigenin, baicalein and curcumin) significantly reduced the repair rate of both types of plasmid substrates. Although this in vitro protocol is only partly representative of the in vivo situation, the natural products appear to interfere with NHEJ repair and warrant further investigation.

Identifiants :
  • DOI : 10.1016/j.mrgentox.2014.04.014

Mots-clés :
  • (Anglais) chemoprevention
  • (Anglais) microelectrophoresis
  • (Anglais) arbutin
  • (Anglais) flavonoids
  • (Anglais) indole-3-carbinol
  • (Anglais) DNA repair
  • (Anglais) arbutin