Plant Sterols as Selective DNA Polymerase Beta Lyase Inhibitors and Potentiators of Bleomycin Cytotoxicity

Bioorg Med Chem. 2004 Aug 1;12(15):4253-8. doi: 10.1016/j.bmc.2004.05.016.


In a survey of crude plant extracts for DNA polymerase beta lyase inhibitors, the hexanes extracts of Cladogynus orientalis, Hymenache donacifolia, and Heteropsis integerrima, and the methyl ethyl ketone extract of Acacia pilispina were found to exhibit good inhibition of the dRP lyase activity of DNA polymerase beta. Bioassay-guided fractionation of these extracts led to the isolation of three DNA polymerase beta lyase inhibitory phytosterols, namely stigmasterol (1) and beta-sitosterol (2), isolated from the hexanes extracts, and beta-sitosterol-beta-d-glucoside (3), isolated from the methyl ethyl ketone extract. Compounds 1-3 inhibited the DNA polymerase beta lyase activity with IC(50) values of 43.6, 43.3, and 72.4 microM, respectively. Compounds 1 and 2 were found capable of potentiating the action of bleomycin in cultured human tumor cells, consistent with the possibility that lyase inhibitors may find utility in vivo.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Bleomycin / agonists*
  • Bleomycin / toxicity
  • Cell Division / drug effects
  • Cell Line
  • DNA Polymerase beta / antagonists & inhibitors*
  • DNA Polymerase beta / metabolism
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Lyases / antagonists & inhibitors*
  • Lyases / metabolism
  • Molecular Sequence Data
  • Phytosterols / isolation & purification
  • Phytosterols / metabolism
  • Phytosterols / pharmacology*


  • Enzyme Inhibitors
  • Phytosterols
  • Bleomycin
  • DNA Polymerase beta
  • Lyases