Inhibition of P-glycoprotein activity and chemosensitization of multidrug-resistant ovarian carcinoma 2780AD cells by hexanoylglucosylceramide

Biochem Biophys Res Commun. 1999 Dec 20;266(2):492-6. doi: 10.1006/bbrc.1999.1850.

Abstract

In the present study we show that neutral hexanoyl-(glyco)sphingolipids inhibit P-glycoprotein (Pgp) activity in human ovarian 2780AD cells. By contrast, hexanoylceramide and the gangliosides GM(3) and GM(2) had no effect on Pgp activity, whereas sphingosine had a stimulating effect. In the case of hexanoylglucosylceramide, inhibition of Pgp activity by was reflected by a regained doxorubicin sensitivity of cells, which were grown in medium supplemented with the lipid. Our results lead to the conclusion that a direct transmodulation of Pgp activity by glycolipids occurs, depending on lipid headgroup structure, which can result in reduced resistance to the chemotherapeutic agent doxorubicin.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple
  • Female
  • Glucosylceramides / pharmacology*
  • Humans
  • Ovarian Neoplasms
  • Rhodamine 123 / metabolism
  • Sphingolipids / pharmacology*
  • Sphingosine / pharmacology
  • Tumor Cells, Cultured

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Glucosylceramides
  • Sphingolipids
  • Rhodamine 123
  • Doxorubicin
  • Sphingosine