Enhanced daunomycin accumulation in human intestinal Caco-2 cells from non-ionic food emulsifiers unrelated to the p-glycoprotein inhibitory mechanism

Biosci Biotechnol Biochem. 2006 Nov;70(11):2703-11. doi: 10.1271/bbb.60306. Epub 2006 Nov 7.


Some of the non-ionic surfactants used in pharmaceutical formulations inhibit P-glycoprotein (P-gp), the multi-drug transporter. The effect of such food emulsifiers as polyglycerol esters (PGE) and sugar esters (SE) of fatty acids on the P-gp activity was studied by using human intestinal Caco-2 cells. The cellular accumulation of [(3)H]-daunomycin, a P-gp substrate, was markedly enhanced by PGE and SE. This accumulation-enhancing activity varied among the emulsifiers, but was correlated with their surface activity. The uptake of soluble nutrients such as amino acids was only slightly reduced by PGE and SE. These results suggest that these emulsifiers specifically inhibited P-gp. When the basal-to-apical transport of daunomycin across the Caco-2 monolayers was measured, however, the emulsifiers did not decrease the efflux of daunomycin to the apical chamber. The enhanced accumulation of daunomycin would therefore not have been due to P-gp inhibition, but instead to the increased daunomycin permeability of cell membranes caused by the emulsifiers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Biological Transport
  • Caco-2 Cells
  • Daunorubicin / metabolism*
  • Emulsifying Agents / pharmacology*
  • Esters / chemistry
  • Food
  • Glycerol / chemistry
  • Humans
  • Intestinal Mucosa / metabolism*
  • Intestines / drug effects*
  • Ions / chemistry
  • Molecular Structure
  • Polymers / chemistry


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Emulsifying Agents
  • Esters
  • Ions
  • Polymers
  • polyglycerol
  • Glycerol
  • Daunorubicin