Structure and Activity Relationship of Monogalactosyl Diacylglycerols, Which Selectively Inhibited in Vitro Mammalian Replicative DNA Polymerase Activity and Human Cancer Cell Growth

Cancer Lett. 2009 Sep 28;283(1):101-7. doi: 10.1016/j.canlet.2009.03.029. Epub 2009 Apr 18.

Abstract

The glycoglycerolipid, monogalactosyl diacylglycerol (MGDG), containing two alpha-linolenic acids (C18:3), was isolated from bitter melon as a potent and selective inhibitor of mammalian DNA polymerase (pol) species such as pols alpha, gamma, delta, and epsilon with IC(50) values of 17.6-37.2muM. This MGDG also suppressed the growth of six human cancer cell lines, although normal human cell lines were not affected. This compound (i.e., MGDG-C18:3-C18:3) was a stronger inhibitor than both MGDG-C18:1-C18:0 and MGDG-C18:0-C18:0. In this study, we discussed the structure-function relationship in the selective inhibition of mammalian replicative pols and human cancer cell proliferation by MGDGs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cattle
  • Cell Line, Tumor
  • Cucurbitaceae / chemistry
  • DNA-Directed DNA Polymerase / drug effects*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Galactolipids / chemistry
  • Galactolipids / isolation & purification
  • Galactolipids / pharmacology*
  • Humans
  • In Vitro Techniques
  • Neoplasms / enzymology*
  • Nucleic Acid Synthesis Inhibitors
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Phytogenic
  • Enzyme Inhibitors
  • Galactolipids
  • Nucleic Acid Synthesis Inhibitors
  • Plant Extracts
  • monogalactosyldiacylglycerol
  • DNA-Directed DNA Polymerase