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

In the present study we show that neutral hexanoyl(glyco)sphingolipids inhi bit P-glycoprotein (Pgp) activity in human ovarian 2780AD cells. By contras t, hexanoylceramide and the gangliosides GM(3) and GM(2) had no effect on P gp activity, whereas sphingosine had a stimulating effect. In the case of h exanoylglucosylceramide, inhibition of Pgp activity by was reflected by a r egained doxorubicin sensitivity of cells, which were grown in medium supple mented with the lipid. Our results lead to the conclusion that a direct tra nsmodulation of Pgp activity by glycolipids occurs, depending on lipid head group structure, which can result in reduced resistance to the chemotherape utic agent doxorubicin. (C) 1999 Academic Press.