A novel DNA polymerase inhibitor and a potent apoptosis inducer: 2-mono-O-acyl-3-O-(alpha-D-sulfoquinovosyl)-glyceride with stearic acid

Biochim Biophys Acta. 2003 Jan 31;1645(1):72-80. doi: 10.1016/s1570-9639(02)00521-6.


Sulfo-glycolipids in the class of sulfoquinovosyl diacylglycerol (SQDG) including the stereoisomers are potent inhibitors of DNA polymerase alpha and beta. However, since the alpha-configuration of SQDG with two stearic acids (alpha-SQDG-C(18)) can hardly penetrate cells, it has no cytotoxic effect. We tried and succeeded in making a permeable form, sulfoquinovosyl monoacylglycerol with a stearic acid (alpha-SQMG-C(18)) from alpha-SQDG-C(18) by hydrolysis with a pancreatic lipase. alpha-SQMG-C(18) inhibited DNA polymerase activity and was found to be a potent inhibitor of the growth of NUGC-3 cancer cells. alpha-SQMG-C(18) arrested the cell cycle at the G1 phase, and subsequently induced severe apoptosis. The arrest was correlated with an increased expression of p53 and cyclin E, indicating that alpha-SQMG-C(18) induced cell death through a p53-dependent apoptotic pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Apoptosis*
  • Cell Cycle / drug effects
  • Cell Membrane Permeability
  • Cyclin E / analysis
  • DNA Polymerase I / antagonists & inhibitors
  • Enzyme Inhibitors / chemistry
  • Glycolipids / chemical synthesis
  • Glycolipids / chemistry*
  • Glycolipids / pharmacology
  • Humans
  • Lipase
  • Molecular Structure
  • Nucleic Acid Synthesis Inhibitors*
  • Stearic Acids / chemistry
  • Tumor Cells, Cultured / drug effects
  • Tumor Suppressor Protein p53 / analysis


  • 2-stearoyl-3-O-sulfoquinovosylglyceride
  • Antineoplastic Agents
  • Cyclin E
  • Enzyme Inhibitors
  • Glycolipids
  • Nucleic Acid Synthesis Inhibitors
  • Stearic Acids
  • Tumor Suppressor Protein p53
  • stearic acid
  • DNA Polymerase I
  • Lipase